Abstract <p><b>Objective:</b> The induction of cellular senescence in ovarian cancer cells has emerged as a promising therapeutic strategy. Olaparib, the first approved PARP inhibitor, is widely used in the treatment of various cancers, including ovarian cancer. This study aimed to investigate the effects of olaparib on the induction of senescence in ovarian cancer cells. <b>Methods:</b> A2780 ovarian cancer cells were treated with olaparib at concentrations of 15, 30, and 60 μM. DNA damage was assessed by measuring levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and γH2AX. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-Gal) staining and telomerase activity assays. Gene and protein expression were analyzed by real-time PCR and Western blotting, respectively. <b>Results and Discussion:</b> Olaparib treatment led to a significant reduction in telomerase activity in A2780 cells. It also induced DNA damage, as evidenced by increased levels of 8-OHdG and γH2AX. Furthermore, olaparib promoted cellular senescence, confirmed by positive SA-β-Gal staining. Treatment with olaparib resulted in decreased expression of hTERT and Lamin B1, both of which are markers associated with cellular proliferation and nuclear integrity, respectively. Notably, olaparib downregulated the expression of SIRT1, a key regulator of cellular senescence, while upregulating acetylation of p53 at lysine 382 (ac-p53^K382) and p21 expression. Overexpression of SIRT1 attenuated olaparib-induced senescence in A2780 cells. <b>Conclusions:</b> These findings reveal a novel pharmacological activity and molecular mechanism of olaparib in promoting senescence in ovarian cancer cells through SIRT1 inhibition.</p>