<PAGE>

                                                                    EXHIBIT 31.1

                                 CERTIFICATION

I, Colin Goddard, certify that:

          1.  I have reviewed this annual report on Form 10-K of OSI
     Pharmaceuticals, Inc.;

          2.  Based on my knowledge, this report does not contain any untrue
     statement of a material fact or omit to state a material fact necessary to
     make the statements made, in light of the circumstances under which such
     statements were made, not misleading with respect to the period covered by
     this report;

          3.  Based on my knowledge, the financial statements, and other
     financial information included in this report, fairly present in all
     material respects the financial condition, results of operations and cash
     flows of the registrant as of, and for, the periods presented in this
     report;

          4.  The registrant's other certifying officer and I are responsible
     for establishing and maintaining disclosure controls and procedures (as
     defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) for the registrant
     and have:

             a) designed such disclosure controls and procedures, or caused such
        disclosure controls and procedures to be designed under our supervision,
        to ensure that material information relating to the registrant,
        including its consolidated subsidiaries, is made known to us by others
        within those entities, particularly during the period in which this
        report is being prepared;

             b) [paragraph omitted pursuant to SEC Release Nos. 33-8238 and
        34-47986];

             c) evaluated the effectiveness of the registrant's disclosure
        controls and procedures and presented in this report our conclusions
        about the effectiveness of the disclosure controls and procedures, as of
        the end of the period covered by this report based on such evaluation;
        and

             d) disclosed in this report any change in the registrant's internal
        control over financial reporting that occurred during the registrant's
        most recent fiscal quarter (the registrant's fourth fiscal quarter in
        the case of an annual report) that has materially affected, or is
        reasonably likely to materially affect, the registrant's internal
        control over financial reporting; and

          5.  The registrant's other certifying officer and I have disclosed,
     based on our most recent evaluation of internal control over financial
     reporting, to the registrant's auditors and the audit committee of the
     registrant's board of directors (or persons performing the equivalent
     functions):

             a) all significant deficiencies and material weaknesses in the
        design or operation of internal control over financial reporting which
        are reasonably likely to adversely affect the registrant's ability to
        record, process, summarize and report financial information; and

             b) any fraud, whether or not material, that involves management or
        other employees who have a significant role in the registrant's internal
        control over financial reporting.

                                          /s/ COLIN GODDARD PH.D.
                                          --------------------------------------
                                          Colin Goddard, Ph.D.
                                          Chief Executive Officer

Date: December 13, 2004