Objective: This study was aimed to investigate the protective effects of polyphenols from Phyllanthus emblica L. (PPE) against ethanol-induced oxidative damage in rats liver cell, and further reveal the molecular mechanisms by examining the Nrf2/HO-1 pathway. Methods: BRL-3A mice were used to evaluate the hepatoprotective effect of PPE on liver injury induced by ethanol exposure. The biochemical parameters (MDA, SOD, ALT, AST and GSH) were measured using commercial kits. HO-1 mRNA level was determined by Q-PCR. Protein levels were measured by western blot. Results: A decreased amount of MDA, ALT and AST release were observed, whereas PPE pretreatment significantly increased the leakage of SOD and GSH in BRL-3A cells. Furthermore, PPE pretreatment apparently up-regulated HO-1 expression, and prevented the overexpression of Nrf2 expressions. Conclusion: These results demonstrate that PPE-mediated up-regulation of HO-1 via Nrf-2 signaling pathway may provide a pivotal mechanism for its hepatoprotective activity. The phenolic compounds including gallic acid, corilagin and ellagic acid present in PPE might be playing a major role against alcohol-induced oxidative damage in rat cells.