Abstract: Objective To investigate the effect of norcantharidin(NCTD) on the apoptosis of human colon carcinoma cells LS-174T and its possible molecular mechanism. Methods MTT assay was used to detect the effects of NCTD on growth inhibition in LS-174T cells. Acridine orang/ ethidium (AO/EB) bromide double staining and transmission electron microscope technique were used to observe the changes of cellular morphology and ultrastructure. AnnexinV/PI staining was used to detect the rate of apoptosis. Western blot was used to assess the protein levels of stat3, survivin, Mcl-1 and bax. Results NCTD signifi cantly inhibited LS-174T cells growth in a time- and dose-dependent manner(5, 10, 20, 40 μg/ml). The maximum inhibition rate was (72.4±3.1)% at 40 μg/ml and 72 h. AO/EB staining and fl ow cytometry showed that with the increase of the concentration of NCTD, apoptosis rate was increased signifi cantly.Transmission electron microscope found signifi cant morphological change of apoptosis; Western blot results showed that the protein expression of stat-3, survivin and Mcl-1 was significantly reduced, whereas the expression of bax was significantly increased. Conclusion NCTD can inhibit the growth of colon cancer cells LS-174T and promote its apoptosis. The mechanism maybe through inhibiting stat3.