In order to unravel the mechanism of inhibition of the cell proliferation induced by overexpression of PEMT2, the cell clone transfected with pemt2-cDNA was constructed and the effect of overexpression of PEMT2 on PI3K/Akt signaling pathway was investigated by the methods of RT-PCR, immunocytochemical and flow cytometry. The results show that the overexpression of PEMT2 could inhibit the expression of PI3K and Akt, and induce cell apoptosis. The results indicate that the down-regulating of PI3K/Akt signaling pathway could, at least partly, account for the inhibition of hepatoma cell proliferation induced by overexpression of PEMT2.