<PAGE>   1
 
                                                      Registration No. 333-_____

      As filed with the Securities and Exchange Commission on May 19, 1998

--------------------------------------------------------------------------------

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
                              -------------------

                                    FORM S-8
                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                               -----------------

                                   HYSEQ, INC.
             (Exact name of registrant as specified in its charter)


          NEVADA                                         36-3855489
(State or other Jurisdiction                          (I.R.S. Employer
of incorporation or organization)                    Identification Number)


670 ALMANOR AVENUE                               (408) 524-8100 
SUNNYVALE, CALIFORNIA 94086                      (Telephone number, including 
(Address, Including Zip Code, of                 area code, of registrant's 
registrant's principal executive offices)        principal executive offices)



               HYSEQ, INC. NON-EMPLOYEE DIRECTOR STOCK OPTION PLAN
                                       AND
                       HYSEQ, INC. STOCK OPTION AGREEMENTS
                            (Full title of the plans)

                               MR. LEWIS S. GRUBER
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                   HYSEQ, INC.
                               670 ALMANOR AVENUE
                           SUNNYVALE, CALIFORNIA 94086

(Name, address, including zip code and telephone number, including area code, of
 agent for service)

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>

------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Title of each                 Amount to be         Proposed maximum       Proposed maximum           Amount of
class of securities           registered(1)       offering price per     aggregate offering     registration fee(2)
to be registered(1)                                    share(2)               price(2)
<S>                        <C>                    <C>                   <C>                    <C> 
------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Common Stock, par value          
$.001 per share                  734,392                 $13.125              $9,638,895               $2,843
------------------------- ---------------------- ---------------------- ---------------------- ----------------------
</TABLE>

 (1) This Registration Statement includes any additional shares of the
registrant's Common Stock that may be issued pursuant to antidilution provisions
contained in the plans.

(2) Pursuant to Rule 457(h), the registration fee was computed on the basis of
the average of the high and low prices of the registrant's Common Stock on the
NASDAQ National Market on May 18, 1998.


<PAGE>   2




                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT


         ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents, which have heretofore been filed by Hyseq,
Inc. (the "Company") with the Securities and Exchange Commission (the
"Commission"), are incorporated by reference in this Registration Statement,
except to the extent that any statement or information therein is modified,
superseded or replaced by a statement or information contained in any other
subsequently filed document incorporated herein by reference:

     i.       the  Company's  prospectus  dated August 7, 1997 filed  pursuant 
              to Rule 424(b) of the  Securities  Act of 1933 included as part 
              of the Company's Registration Statement on Form S-1 (No. 333-
              29091);

     ii.      the Company's Annual Report on Form 10-K for the year ended 
              December 31, 1997;

     iii.     the Company's Quarterly Report on Form 10-Q for the period ended 
              March 31, 1998; and

     iv.      the description of the Company's Common Stock contained in the
              Company's Registration Statement on Form 8-A, dated July 23, 1997.

All documents filed by the Company or the plans pursuant to Sections 13(a),
13(c), 14 and 15(d) of the Exchange Act after the date hereof, and prior to the
filing of a post-effective amendment which indicates that all securities offered
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference herein and to be a part hereof from
the date of filing of such documents.

         ITEM 4.  DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Not applicable.

         ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         As permitted by the Nevada General Corporation Law, the Company's
Articles and By-Laws provide that officers and directors of the Company shall
not be personally liable for monetary 

                                       2

<PAGE>   3


damages to the Company for certain breaches of their fiduciary duty as
directors, unless they violated their duty of loyalty to the Company or its
stockholders, acted in bad faith, knowingly or intentionally violated the law,
authorized illegal dividends or redemptions, or derived an improper personal
benefit from their action as directors. This provision would have no effect on
the availability of equitable remedies or nonmonetary relief, such as an
injunction or rescission for breach of the duty of care. Directors will,
however, no longer be liable for monetary damages arising from decisions
involving violations of the duty of care which could be deemed grossly
negligent.

         The By-Laws provide that directors of the Company shall be indemnified
by the Company to the fullest extent authorized by Nevada law, as it now exists
or may in the future be amended, against all expenses and liabilities reasonably
incurred in connection with service for or on behalf of the Company. The By-Laws
also authorize the Company to enter into one or more agreements with any person
which provide for indemnification greater or different from that provided in the
Articles. The Company has entered into indemnification agreements with all
current officers and members of the Board of Directors. Insofar as
indemnification for liabilities arising under the Securities Act may be
permitted to directors, officers and controlling persons of the Company pursuant
to the foregoing provisions, or otherwise, the Company has been advised that in
the opinion of the Commission such indemnification is against public policy as
expressed in the Securities Act and is, therefore, unenforceable.

         ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8.  EXHIBITS.

         See Exhibit Index which is incorporated herein by reference.

         ITEM 9.  UNDERTAKINGS.

         (a)      The undersigned registrant hereby undertakes:

                 (1)      To file,  during any period in which  offers or sales
                          are being made, a  post-effective  amendment to this
                          registration statement:

                          i.       To include any prospectus  required by 
                                   Section  10(a)(3) of the  Securities  Act of
                                   1933 (the  "Securities Act");

                          ii.       To reflect in the prospectus any facts or
                                    events arising after the effective date of
                                    the registration statement (or the most
                                    recent post-effective amendment thereof)
                                    which, individually or in the aggregate,
                                    represent a fundamental change in the
                                    information set forth in the registration
                                    statement;


                                       3

                                       
<PAGE>   4



                          iii.      To include any material information with
                                    respect to the plan of distribution not
                                    previously disclosed in the registration
                                    statement or any material change to such
                                    information in the registration statement;

                          Provided,however, that paragraphs (a)(1)(i) and (a)(1)
                          (ii) do not apply if the registration statement is on 
                          Form S-3 or Form S-8, and the information required to 
                          be included in a post-effective amendment by those
                          paragraphs is contained in periodic reports filed by
                          the registrant pursuant to Section 13 or Section
                          15(d) of the Exchange Act that are incorporated by
                          reference in the registration statement.

                   (2)    That, for the purpose of determining any liability
                          under the Securities Act, each such post-effective
                          amendment shall be deemed to be a new registration
                          statement relating to the securities offered therein,
                          and the offering of such securities at that time
                          shall be deemed to be the initial bona fide offering
                          thereof.

                   (3)    To remove from registration by means of a
                          post-effective amendment any of the securities being
                          registered which remain unsold at the termination of
                          the offering.

         (b)      The undersigned registrant hereby undertakes that, for
                  purposes of determining any liability under the Securities Act
                  of 1933, each filing of the registrant's annual report
                  pursuant to Section 13(a) or Section 15(d) of the Exchange Act
                  and each filing of the plans' annual report pursuant to
                  Section 15(d) of the Exchange Act that is incorporated by
                  reference in the registration statement shall be deemed to be
                  a new registration statement relating to the securities
                  offered therein, and the offering of such securities at that
                  time shall be deemed to be the initial bona fide offering
                  thereof.

         (c)      Insofar  as  indemnification  for  liabilities  arising  under
                  the  Securities  Act may be  permitted  to officers,  
                  directors,  and  controlling  persons of the registrant  
                  pursuant to the  registrant's certificate of  incorporation or
                  by-laws,  or otherwise,  the registrant has been advised that
                  in the opinion of the Commission such  indemnification  is 
                  against public policy as expressed in the Securities Act and 
                  is, therefore,  unenforceable.  In the event that a claim for
                  indemnification against such liabilities  (other than the 
                  payment by the registrant of expenses  incurred or paid
                  by a director,  officer or controlling  person of the 
                  registrant in the successful defense of any action,  suit or 
                  proceeding)  is asserted by such director,  officer,  or 
                  controlling  person in connection with the securities being 
                  registered,  the registrant will,  unless in the opinion of
                  its  counsel  the  matter  has  been  settled  by  controlling
                  precedent,  submit  to a court of appropriate  jurisdiction  
                  the question  whether  such  indemnification  by it is 
                  against public policy as  expressed  in the Securities Act 
                  and will be governed by the final  adjudication  of such 
                  issue.


                                        4


                                      
<PAGE>   5


                                   SIGNATURES

         THE REGISTRANT. Pursuant to the requirements of the Securities Act of
1933, the registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this
registration statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of May, 1998.

                                                   Hyseq, Inc.


                                      By:  /s/ Lewis S. Gruber
                                           -------------------------------------
                                           Lewis S. Gruber
                                           President and Chief Executive Officer





                                       5

<PAGE>   6


                                POWER OF ATTORNEY

         Know all men by these presents, that each person whose signature
appears below constitutes and appoints Lewis S. Gruber and Christopher R. Wolf,
and each of them singly, his true and lawful attorneys-in-fact and agents, with
full power of substitution and resubstitution, for him and in his name, place
and stead, in any and all capacities (including his capacity as a director
and/or officer of Hyseq, Inc.) to sign any and all amendments (including
post-effective amendments) to this Registration Statement, and to file the same,
with all exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in and about the
premises, as fully to all intents and purposes as he might or could do in
person, hereby ratifying and confirming all that said attorneys-in-fact and
agents or any of them, or their or his substitute or substitutes, may lawfully
do or cause to be done by virtue thereof.

         IN WITNESS WHEREOF, the undersigned have executed this power of
attorney on the 18th day of May, 1998.

<TABLE>
<CAPTION>
<S>                                                         <C>
/s/ Robert D. Weist                                           /s/ Lewis S. Gruber
-------------------                                           -------------------
Robert D. Weist                                               Lewis S. Gruber


/s/ Christopher R. Wolf                                       /s/ Radomir B. Crkvenjakov, Ph.D.
-----------------------                                       ---------------------------------
Christopher R. Wolf                                           Radomir B. Crkvenjakov, Ph.D.


/s/ Radoje T. Drmanac, Ph.D.                                  /s/ Greta E. Marshall
----------------------------                                  ---------------------
Radoje T. Drmanac, Ph.D.                                      Greta E. Marshall


/s/ Raymond F. Baddour, Ph.D.                                 /s/ Kenneth D. Noonan, Ph.D.
-----------------------------                                 ----------------------------
Raymond F. Baddour, Ph.D.                                     Kenneth D. Noonan, Ph.D.


/s/ Thomas N. McCarter III
--------------------------
Thomas N. McCarter III

</TABLE>



                                       6


<PAGE>   7


         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in their
respective capacities on this 18th day of May, 1998.

<TABLE>
<CAPTION>


         Signature                                                      Title
         ---------                                                      -----
<S>                                               <C>

/s/ Robert D. Weist
-------------------
Robert D. Weist                                      Chairman of the Board of Directors


/s/ Lewis S. Gruber
-------------------
Lewis S. Gruber                                      President and Chief Executive Officer and Director
                                                     (Principal Executive Officer)


/s/ Christopher R. Wolf
-----------------------
Christopher R. Wolf                                  Executive Vice President and Chief Financial Officer
                                                     (Principal Financial and Accounting Officer)


/s/ Radoje T. Drmanac, Ph.D.
----------------------------
Radoje T. Drmanac, Ph.D.                             Co-Senior Vice President for Research and Director


/s/ Radomir B. Crkvenjakov, Ph.D.
---------------------------------
Radomir B. Crkvenjakov, Ph.D.                        Co-Senior Vice President for Research and Director


/s/ Raymond F. Baddour, Ph.D.
-----------------------------
Raymond F. Baddour, Ph.D.                            Director


/s/ Greta E. Marshall
---------------------
Greta E. Marshall                                    Director


/s/ Thomas N. McCarter III
--------------------------
Thomas N. McCarter III                               Director


/s/ Kenneth D. Noonan, Ph.D.
----------------------------
Kenneth D. Noonan, Ph.D.                             Director

</TABLE>


                                       7

<PAGE>   8


                                  EXHIBIT INDEX

<TABLE>
<CAPTION>

        Exhibit
         Number                                   Description of Exhibit
         ------                                   ----------------------

<S>                      <C>
          4.1             Certificate of Incorporation of Hyseq, Inc. as amended to date*

          4.2             By-Laws of Hyseq, Inc., as amended to date*

          4.3             Hyseq, Inc. Non-Employee Director Stock Option Plan

          4.4             Hyseq, Inc. Stock Option Agreement

           5              Opinion of Sachnoff & Weaver, Ltd.

           23             Consent of Ernst & Young LLP, Independent Auditors

           24             Powers of Attorney (contained on the page prior to the signature page
                          hereto)
</TABLE>

------------------------------


*        Filed as an exhibit to the Company's Registration Statement on Form
         S-1 (Registration Statement No. 333-29091) declared effective by the
         Securities and Exchange Commission on August 7, 1997, and incorporated
         herein by reference.



                                      8
[{"type": "S-8", "sequence": "1", "description": "NON-EMPLOYEE DIRECTOR STOCK OPTION PLAN", "secsgml_size_bytes": 19297}]
{"company-data": {"conformed-name": "HYSEQ INC", "cik": "0000907654", "assigned-sic": "2835", "irs-number": "363855489", "state-of-incorporation": "NV", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-53089", "film-number": "98628426"}, "business-address": {"street1": "670 ALMANOR AVE", "city": "SUNNYVALE", "state": "CA", "zip": "94086", "phone": "4085248100"}, "mail-address": {"street1": "670 ALMANOR AVE", "city": "SUNNYVALE", "state": "CA", "zip": "94086"}}
1
 
                                                      Registration No. 333-_____

      As filed with the Securities and Exchange Commission on May 19, 1998

--------------------------------------------------------------------------------

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
                              -------------------

                                    FORM S-8
                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                               -----------------

                                   HYSEQ, INC.
             (Exact name of registrant as specified in its charter)

          NEVADA                                         36-3855489
(State or other Jurisdiction                          (I.R.S. Employer
of incorporation or organization)                    Identification Number)

670 ALMANOR AVENUE                               (408) 524-8100 
SUNNYVALE, CALIFORNIA 94086                      (Telephone number, including 
(Address, Including Zip Code, of                 area code, of registrant's 
registrant's principal executive offices)        principal executive offices)

               HYSEQ, INC. NON-EMPLOYEE DIRECTOR STOCK OPTION PLAN
                                       AND
                       HYSEQ, INC. STOCK OPTION AGREEMENTS
                            (Full title of the plans)

                               MR. LEWIS S. GRUBER
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                   HYSEQ, INC.
                               670 ALMANOR AVENUE
                           SUNNYVALE, CALIFORNIA 94086

(Name, address, including zip code and telephone number, including area code, of
 agent for service)

                         CALCULATION OF REGISTRATION FEE
------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Title of each                 Amount to be         Proposed maximum       Proposed maximum           Amount of
class of securities           registered(1)       offering price per     aggregate offering     registration fee(2)
to be registered(1)                                    share(2)               price(2)
------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Common Stock, par value          
$.001 per share                  734,392                 $13.125              $9,638,895               $2,843
------------------------- ---------------------- ---------------------- ---------------------- ----------------------
(1) This Registration Statement includes any additional shares of the
registrant's Common Stock that may be issued pursuant to antidilution provisions
contained in the plans.

(2) Pursuant to Rule 457(h), the registration fee was computed on the basis of
the average of the high and low prices of the registrant's Common Stock on the
NASDAQ National Market on May 18, 1998.
2

                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT

         ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents, which have heretofore been filed by Hyseq,
Inc. (the "Company") with the Securities and Exchange Commission (the
"Commission"), are incorporated by reference in this Registration Statement,
except to the extent that any statement or information therein is modified,
superseded or replaced by a statement or information contained in any other
subsequently filed document incorporated herein by reference:

     i.       the  Company's  prospectus  dated August 7, 1997 filed  pursuant 
              to Rule 424(b) of the  Securities  Act of 1933 included as part 
              of the Company's Registration Statement on Form S-1 (No. 333-
              29091);

     ii.      the Company's Annual Report on Form 10-K for the year ended 
              December 31, 1997;

     iii.     the Company's Quarterly Report on Form 10-Q for the period ended 
              March 31, 1998; and

     iv.      the description of the Company's Common Stock contained in the
              Company's Registration Statement on Form 8-A, dated July 23, 1997.

All documents filed by the Company or the plans pursuant to Sections 13(a),
13(c), 14 and 15(d) of the Exchange Act after the date hereof, and prior to the
filing of a post-effective amendment which indicates that all securities offered
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference herein and to be a part hereof from
the date of filing of such documents.

         ITEM 4.  DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Not applicable.

         ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         As permitted by the Nevada General Corporation Law, the Company's
Articles and By-Laws provide that officers and directors of the Company shall
not be personally liable for monetary 

                                       2
3

damages to the Company for certain breaches of their fiduciary duty as
directors, unless they violated their duty of loyalty to the Company or its
stockholders, acted in bad faith, knowingly or intentionally violated the law,
authorized illegal dividends or redemptions, or derived an improper personal
benefit from their action as directors. This provision would have no effect on
the availability of equitable remedies or nonmonetary relief, such as an
injunction or rescission for breach of the duty of care. Directors will,
however, no longer be liable for monetary damages arising from decisions
involving violations of the duty of care which could be deemed grossly
negligent.

         The By-Laws provide that directors of the Company shall be indemnified
by the Company to the fullest extent authorized by Nevada law, as it now exists
or may in the future be amended, against all expenses and liabilities reasonably
incurred in connection with service for or on behalf of the Company. The By-Laws
also authorize the Company to enter into one or more agreements with any person
which provide for indemnification greater or different from that provided in the
Articles. The Company has entered into indemnification agreements with all
current officers and members of the Board of Directors. Insofar as
indemnification for liabilities arising under the Securities Act may be
permitted to directors, officers and controlling persons of the Company pursuant
to the foregoing provisions, or otherwise, the Company has been advised that in
the opinion of the Commission such indemnification is against public policy as
expressed in the Securities Act and is, therefore, unenforceable.

         ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8.  EXHIBITS.

         See Exhibit Index which is incorporated herein by reference.

         ITEM 9.  UNDERTAKINGS.

         (a)      The undersigned registrant hereby undertakes:

                 (1)      To file,  during any period in which  offers or sales
                          are being made, a  post-effective  amendment to this
                          registration statement:

                          i.       To include any prospectus  required by 
                                   Section  10(a)(3) of the  Securities  Act of
                                   1933 (the  "Securities Act");

                          ii.       To reflect in the prospectus any facts or
                                    events arising after the effective date of
                                    the registration statement (or the most
                                    recent post-effective amendment thereof)
                                    which, individually or in the aggregate,
                                    represent a fundamental change in the
                                    information set forth in the registration
                                    statement;

                                       3
4

                          iii.      To include any material information with
                                    respect to the plan of distribution not
                                    previously disclosed in the registration
                                    statement or any material change to such
                                    information in the registration statement;

                          Provided,however, that paragraphs (a)(1)(i) and (a)(1)
                          (ii) do not apply if the registration statement is on 
                          Form S-3 or Form S-8, and the information required to 
                          be included in a post-effective amendment by those
                          paragraphs is contained in periodic reports filed by
                          the registrant pursuant to Section 13 or Section
                          15(d) of the Exchange Act that are incorporated by
                          reference in the registration statement.

                   (2)    That, for the purpose of determining any liability
                          under the Securities Act, each such post-effective
                          amendment shall be deemed to be a new registration
                          statement relating to the securities offered therein,
                          and the offering of such securities at that time
                          shall be deemed to be the initial bona fide offering
                          thereof.

                   (3)    To remove from registration by means of a
                          post-effective amendment any of the securities being
                          registered which remain unsold at the termination of
                          the offering.

         (b)      The undersigned registrant hereby undertakes that, for
                  purposes of determining any liability under the Securities Act
                  of 1933, each filing of the registrant's annual report
                  pursuant to Section 13(a) or Section 15(d) of the Exchange Act
                  and each filing of the plans' annual report pursuant to
                  Section 15(d) of the Exchange Act that is incorporated by
                  reference in the registration statement shall be deemed to be
                  a new registration statement relating to the securities
                  offered therein, and the offering of such securities at that
                  time shall be deemed to be the initial bona fide offering
                  thereof.

         (c)      Insofar  as  indemnification  for  liabilities  arising  under
                  the  Securities  Act may be  permitted  to officers,  
                  directors,  and  controlling  persons of the registrant  
                  pursuant to the  registrant's certificate of  incorporation or
                  by-laws,  or otherwise,  the registrant has been advised that
                  in the opinion of the Commission such  indemnification  is 
                  against public policy as expressed in the Securities Act and 
                  is, therefore,  unenforceable.  In the event that a claim for
                  indemnification against such liabilities  (other than the 
                  payment by the registrant of expenses  incurred or paid
                  by a director,  officer or controlling  person of the 
                  registrant in the successful defense of any action,  suit or 
                  proceeding)  is asserted by such director,  officer,  or 
                  controlling  person in connection with the securities being 
                  registered,  the registrant will,  unless in the opinion of
                  its  counsel  the  matter  has  been  settled  by  controlling
                  precedent,  submit  to a court of appropriate  jurisdiction  
                  the question  whether  such  indemnification  by it is 
                  against public policy as  expressed  in the Securities Act 
                  and will be governed by the final  adjudication  of such 
                  issue.

                                        4
5

                                   SIGNATURES

         THE REGISTRANT. Pursuant to the requirements of the Securities Act of
1933, the registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this
registration statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of May, 1998.

                                                   Hyseq, Inc.

                                      By:  /s/ Lewis S. Gruber
                                           -------------------------------------
                                           Lewis S. Gruber
                                           President and Chief Executive Officer

                                       5
6

                                POWER OF ATTORNEY

         Know all men by these presents, that each person whose signature
appears below constitutes and appoints Lewis S. Gruber and Christopher R. Wolf,
and each of them singly, his true and lawful attorneys-in-fact and agents, with
full power of substitution and resubstitution, for him and in his name, place
and stead, in any and all capacities (including his capacity as a director
and/or officer of Hyseq, Inc.) to sign any and all amendments (including
post-effective amendments) to this Registration Statement, and to file the same,
with all exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in and about the
premises, as fully to all intents and purposes as he might or could do in
person, hereby ratifying and confirming all that said attorneys-in-fact and
agents or any of them, or their or his substitute or substitutes, may lawfully
do or cause to be done by virtue thereof.

         IN WITNESS WHEREOF, the undersigned have executed this power of
attorney on the 18th day of May, 1998.
/s/ Robert D. Weist                                           /s/ Lewis S. Gruber
-------------------                                           -------------------
Robert D. Weist                                               Lewis S. Gruber

/s/ Christopher R. Wolf                                       /s/ Radomir B. Crkvenjakov, Ph.D.
-----------------------                                       ---------------------------------
Christopher R. Wolf                                           Radomir B. Crkvenjakov, Ph.D.

/s/ Radoje T. Drmanac, Ph.D.                                  /s/ Greta E. Marshall
----------------------------                                  ---------------------
Radoje T. Drmanac, Ph.D.                                      Greta E. Marshall

/s/ Raymond F. Baddour, Ph.D.                                 /s/ Kenneth D. Noonan, Ph.D.
-----------------------------                                 ----------------------------
Raymond F. Baddour, Ph.D.                                     Kenneth D. Noonan, Ph.D.

/s/ Thomas N. McCarter III
--------------------------
Thomas N. McCarter III
6
7

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in their
respective capacities on this 18th day of May, 1998.
Signature                                                      Title
         ---------                                                      -----
/s/ Robert D. Weist
-------------------
Robert D. Weist                                      Chairman of the Board of Directors

/s/ Lewis S. Gruber
-------------------
Lewis S. Gruber                                      President and Chief Executive Officer and Director
                                                     (Principal Executive Officer)

/s/ Christopher R. Wolf
-----------------------
Christopher R. Wolf                                  Executive Vice President and Chief Financial Officer
                                                     (Principal Financial and Accounting Officer)

/s/ Radoje T. Drmanac, Ph.D.
----------------------------
Radoje T. Drmanac, Ph.D.                             Co-Senior Vice President for Research and Director

/s/ Radomir B. Crkvenjakov, Ph.D.
---------------------------------
Radomir B. Crkvenjakov, Ph.D.                        Co-Senior Vice President for Research and Director

/s/ Raymond F. Baddour, Ph.D.
-----------------------------
Raymond F. Baddour, Ph.D.                            Director

/s/ Greta E. Marshall
---------------------
Greta E. Marshall                                    Director

/s/ Thomas N. McCarter III
--------------------------
Thomas N. McCarter III                               Director

/s/ Kenneth D. Noonan, Ph.D.
----------------------------
Kenneth D. Noonan, Ph.D.                             Director
7
8

                                  EXHIBIT INDEX
Exhibit
         Number                                   Description of Exhibit
         ------                                   ----------------------
4.1             Certificate of Incorporation of Hyseq, Inc. as amended to date*

          4.2             By-Laws of Hyseq, Inc., as amended to date*

          4.3             Hyseq, Inc. Non-Employee Director Stock Option Plan

          4.4             Hyseq, Inc. Stock Option Agreement

           5              Opinion of Sachnoff & Weaver, Ltd.

           23             Consent of Ernst & Young LLP, Independent Auditors

           24             Powers of Attorney (contained on the page prior to the signature page
                          hereto)
------------------------------

*        Filed as an exhibit to the Company's Registration Statement on Form
         S-1 (Registration Statement No. 333-29091) declared effective by the
         Securities and Exchange Commission on August 7, 1997, and incorporated
         herein by reference.

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