Objective To investigate the effects and mechanisms of sulindac, a non-selective cyclooxygenase(COX)inhibitor, on the proliferation and apoptosis of colorectal cancer cell line HT-29.Methods HT-29 cells were treated with sulindac. MTT assay and flow cytometry were used to measure the proliferation and apoptosis respectively. The laser scanning microscope(LSM)and the fluorescence microscope were used to observe apoptosis of the cells, and the flow cytometry (FCM)analysis was used to observe the cell apoptosis and cell cycle. Results Sulindac inhibited the cells proliferation and induced apoptosis in a dose-and time-dependent manner. With the TUNEL staining and fluorescence microscope, we found that the apoptosis cell became brown. After the Annexin V/PI staining, we observed that the membrane of apoptosis cells became green with LSM; the nucleosidase became red or crocus. FCM showed that sulindac promoted apoptosis of the cells, made the stage of G0/G1 ceils significantly reduced. Conclusions Our results showed that sulindac may inhibit the proliferation and induced the apoptosis of colon cancer cell HT-29,and the mechanism may probably be related to cell cycle arrest.