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Background: The amount of COX-2 increases in most cancers due to synthesis of prostaglandins. Therefore, COX-2 inhibitors may play an effective role in cancer therapy. The goal of this study was to investigate the effect of ibuprofen and indomethacin, as anti-inflammatory drugs, on the K562 cell growth and proliferation. Methods: The K562 cells were cultured and treated with different concentrations of indomethacin and ibuprofen. Then, their antitumor effects on K562 cells was assessed via MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] after 72 hours. DAPI staining (4',6-diamidino-2-phenylindole) and DNA electrophoresis were used for study of  apoptosis. Findings: Ibuprofen and indomethacin had antitumor effect on K562 and this effect increased by raise of time and concentration; so, the maximum of inhibitory effect was observed in higher concentration and 72 hours after the treatment. Statistical analysis indicated that both drugs inhibited the growth of K562 cells (P < 0.05). Conclusion: Based on the results, ibuprofen and indomethacin are effective agents for chronic myeloid leukemia therapy and prevention; but these antitumor properties would warrant further studies on the clinical application.