Abstract: Objective To investigate the effect of PTEN on the apoptosis of hepatoma carcinoma cell line induced by arsenic trioxide(As₂O₃).Methods The effects of As₂O₃ on the cell proliferation was measured by methyl thiazolyl tetrazolium(MTT),apoptosis was determined by flow cytometry,and the expression of PTEN protein was measured by western blot,and the effect of PTEN inhibition by siRNA on apoptosis of As₂O₃-treated SMMC-7721 cells was also examined.Results As₂O₃ inhibited the proliferation of SMMC-7721 cells in a dose dependent manner.As₂O₃ also induced apoptosis in a dose dependent manner.As₂O₃ significantly increased PTEN expression.Transfecting cells with PTEN siRNA significantly attenuated the induced apoptosis by As₂O₃.Conclusion It is suggested that As₂O₃ could induce the apoptosis of SMMC-7721 cells via upregulating PTEN.