Objective: To verify that Proliverenol has a potential ability in protecting cells from ethanol-induced hepatotoxicity. Methods: Activity of Proliverenol against ethanol-induced apoptosis was evaluated at mRNA and protein levels in HepG2 cell exposed to Proliverenol for 1 and 3 h. Results: Proliverenol conferred hepatoprotective activity through increasing cell survival up to 53%-69% via up-regulation of APEX1 DNA repair enzyme for 3.0-4.7 fold and down-regulating of nuclear factor-kB, tumor necrosis factorα and caspase-8 expression, allowing them to prevent 4.5-6.9 fold of alanine aminotransferase (ALT) leakage in HepG2 cells. Our finding revealed that Proliverenol repressed expression of ALT, which is significantly important as possible altative mechanism for increased blood transaminase activities. In addition, the result also showed that caspase-8 pathway seemed to be involved in the molecular pathway rather than directly inducing mitochondrial damage. Conclusions: The data support our hypothesis that Proliverenol has a potential ability in protecting cells from ethanol-induced hepatotoxicity. We propose that Proliverenol pro-vides hepatoprotective activity through up-regulating expression of APEX1 that repress DNA fragmentation, and down-regulating expression of nuclear factor-kB, tumor ne-crosis factorαand caspase-8, which therefore repress ALT leakage and its expression.