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Background and Objectives: Studies have shown that drugs can affect on proliferation of cancer cells. The main aim of this study was to determine the effects of diclofenac on caspase-8 and caspase-9 activity in cervical cancer cells (HeLa) in cell culture. &nbsp; Methods: In this experimental-laboratory study, HeLa cancer cells were purchased from Iran Cell Bank (Pasteur Institute, Tehran, Iran). HeLa cancer cells were cultured in DMEM culture media enriched with 10% FBS, stored in 6 well plate, and incubated for 24 hour. Then, cells were exposed to different concentrations of diclofenac and the viability of cells was evaluated by MTT assay, and the IC50 dose was calculated. The activity of Caspase-8 and caspase-9 on heLa cells, was assayed by ELISA method. The data were analyzed using one-way analysis of variance, Kolmogorov-Smirnov, and Tukey tests. &nbsp; Results: Findings showed that 0.1, 1, and 10mg/ml doses of diclofenac decrease the viability of HeLa cancer cells compared to the control group (p<0.05, p<0.001, and p<0.001, respectively). The percentage of caspase-9 activity was significantly higher than the control group (p<0.05). The caspase-8 activity had no significant change compared to the control group (p>0.05). &nbsp; Conclusion: The results of this study revealed that diclofenac has cytotoxic effects on HeLa cancer cells. Although ths effect is different based on the dose used. &nbsp; &nbsp;