Abstract: Objective To explore the effect of sodium cantharidinate on the apoptosis and expression of p53upregulated modulator of apoptosis（PUMA）of colon cancer cell line. Methods The colon cancer HCT116 cells were treated with different concentrations of sodium cantharidinate（0.1，0.25，0.5，1，2 μg／ml） for 24 h, and control group without sodium cantharidinate was set. The transepithelial electrical resistance（TER）was analyzed to evaluate the influence of sodium cantharidinate on the apoptosis of HCT116 cell. Real-time fluorescence quantitative PCR and Western blotting were used to detect the changes of mRNA and protein level of PUMA in HCT116 cells. The protein level of PUMA was measured by Western blotting in HCT116 cells treated with inhibitor of nuclear factor（NF）-κB（BAY 11-7082）at concentrations of 10，20，40，80 nmol／L or plasmid for inhibitor of NF-κB kinase β（IKKβ）transfection at concentrations of 0.05，0.1，0.2，0.4，0.8 μg／ml. Results There were decreased TER but increased mRNA and protein level of PUMA in different concentrations of sodium cantharidinate versus control group（P＜0.05）. Compared with the untreated HCT116 cells，transfection with IKKβ plasmid increased the protein expression of PUMA，and while NF-κB inhibitor reduced the effect of sodium cantharidinate up-regulating the PUMA level with significance difference （P＜0.05）. Conclusion Sodium cantharidinate may promote the PUMA expression via NF-κB pathway，and therefore induce the apoptosis of HCT116 cells.