Abstract: 【Objective】 To investigate the inhibition mechanism of sodium selenite on HCT116 cells. 【Methods】 In the present study, we explored the cytotoxicity induced by sodium selenite and the underlying mechanism by MTS assay, WesternBlot, and small RNA interference technique. 【Results】 It was found that the sodium selenite at 5uM concentration could indeed reduce the viability of colon cancer cell line HCT116 by a large margin through increasing the generation of reactive oxygen species (ROS), and that the increased levels of ROS could activate c-Jun Nh2-terninal kinase 1 (JNK1).Additionally, knockdown expression of JNK1 or p53 by using RNAi attenuated the cytotoxicity induced by sodium selenite, indicating that both of JNK1 and p53 are required in the process of cell death induced by sodium selenite. 【Conclusion】 The sodium selenite could induces cell death in HCT116 through oxidative stress by involvement of JNK1 and p53, both of which play a critical role in toxicity of sodium selenite.