<PAGE>   1
                                                      Registration No. 333-_____

    As filed with the Securities and Exchange Commission on December 5, 1997
================================================================================

                       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. STOCK OPTION PLAN
                            (Full title of the plan)

                            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                                           Proposed maximum        Proposed maximum
class of securities             Amount to be            offering price per      aggregate offering      Amount of
to be registered(1)             registered(1)           share(2)                price(2)                registration fee(2)
----------------------------------------------------------------------------------------------------------------------------
<S>                             <C>                     <C>                   <C>                    <C>
Common Stock, par
value $.001 per
share                           1,152,000                $11.9375               $13,752,000.00          $4,056.84
----------------------------------------------------------------------------------------------------------------------------
</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 plan.

(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 December 4, 1997.

<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 Quarterly Reports on Form 10-Q for the quarters
          ended June 30, 1997 and September 30, 1997; and

     iii. 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 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

                                       2



<PAGE>   3

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;

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

                                       3



<PAGE>   4

                     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 plan's
          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 4th day of December, 1997.

                                     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 4th day of December, 1997.


                          

                                      /s/ Lewis S. Gruber
------------------------------        -----------------------------------    
Robert D. Weist                       Lewis S. Gruber
                                                                             
                                                                             
/s/ Christopher R. Wolf               /s/ Radomir B. Crkvenjakov
------------------------------        -----------------------------------    
Christopher R. Wolf                   Radomir B. Crkvenjakov, Ph.D.         
                                                                             
                                                                             
/s/ Radoje T. Drmanac                 /s/ Greta E. Marshall                  
------------------------------        -----------------------------------    
Radoje T. Drmanac, Ph.D.              Greta E. Marshall                      
                                                                             
                                                                             
/s/ Raymond F. Baddour                /s/ Kenneth D. Noonan                  
------------------------------        -----------------------------------
Raymond F. Baddour, Ph.D.             Kenneth D. Noonan, Ph.D.               
                                                                             
                                                                             
/s/ Thomas N. McCarter III                                                   
------------------------------                                                 
Thomas N. McCarter III                                                       



                                      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 4th day of December, 1997.                       

<TABLE>
<CAPTION>                                                                               
     Signature                                                  Title
     ---------                                                  -----
<S>                                             <C>                                           
-----------------------------                                                                               
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
-----------------------------
Radoje T. Drmanac, Ph.D.                        Co-Senior Vice President for Research and Director


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


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


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


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


/s/ Kenneth D. Noonan
-----------------------------
Kenneth D. Noonan, Ph.D.                        Director
</TABLE>



                                       7



<PAGE>   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. Stock Option Plan
  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.



                                       8
[{"type": "S-8", "sequence": "1", "description": "REGISTRATION STATEMENT", "secsgml_size_bytes": 19007}]
{"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": "333-41663", "film-number": "97733527"}, "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 December 5, 1997
================================================================================

                       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. STOCK OPTION PLAN
                            (Full title of the plan)

                            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                                           Proposed maximum        Proposed maximum
class of securities             Amount to be            offering price per      aggregate offering      Amount of
to be registered(1)             registered(1)           share(2)                price(2)                registration fee(2)
----------------------------------------------------------------------------------------------------------------------------
Common Stock, par
value $.001 per
share                           1,152,000                $11.9375               $13,752,000.00          $4,056.84
----------------------------------------------------------------------------------------------------------------------------
(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 plan.

(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 December 4, 1997.
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 Quarterly Reports on Form 10-Q for the quarters
          ended June 30, 1997 and September 30, 1997; and

     iii. 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 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

                                       2
3

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;

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

                                       3
4

                     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 plan's
          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 4th day of December, 1997.

                                     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 4th day of December, 1997.

                          

                                      /s/ Lewis S. Gruber
------------------------------        -----------------------------------    
Robert D. Weist                       Lewis S. Gruber
                                                                             
                                                                             
/s/ Christopher R. Wolf               /s/ Radomir B. Crkvenjakov
------------------------------        -----------------------------------    
Christopher R. Wolf                   Radomir B. Crkvenjakov, Ph.D.         
                                                                             
                                                                             
/s/ Radoje T. Drmanac                 /s/ Greta E. Marshall                  
------------------------------        -----------------------------------    
Radoje T. Drmanac, Ph.D.              Greta E. Marshall                      
                                                                             
                                                                             
/s/ Raymond F. Baddour                /s/ Kenneth D. Noonan                  
------------------------------        -----------------------------------
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 4th day of December, 1997.
Signature                                                  Title
     ---------                                                  -----
-----------------------------                                                                               
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
-----------------------------
Radoje T. Drmanac, Ph.D.                        Co-Senior Vice President for Research and Director

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

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

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

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

/s/ Kenneth D. Noonan
-----------------------------
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. Stock Option Plan
  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.

                                       8