Abstract: OBJECTIVE To investigate the inhibitory effect of chelerythrine(CHE) on the growth of colorectal cancer cells in vitro and explore its mechanism. METHODS MTT assay was used to determine the survival rate of colon cancer cells, and flow cytometry was applied to detect reactive oxygen species(ROS) accumulation and apoptosis after CHE treatment. JC-1 fluorescent method was adopted to detect cellular mitochondria potentials while using fluorescent microscope and Western blotting method to validate that accumulation of ROS inducing mitochondrial dysfunction. RESULTS CHE had a dose-dependent cytotoxic effect on HCT-116 and RKO cells, which was related to the expression of ROS mediated apoptosis proteins. In addition, CHE could reduce the mitochondrial membrane potential associated with mitochondrial dysfunction. CONCLUSION CHE inhibits cell growth and induces CRC cell apoptosis through ROS mediated mitochondrial dysfunction and JNKs pathway, suggesting CHE may be a potential candidate drug for CRC therapy.