Alpinia oxyphylla Miq. (A. oxyphylla), as a kind of medicine which also be used as food, is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain and deficiency cold of spleen and stomach. This study aimed to investigate the protective effects of ethanol extract (EE) and its dichloromethane fraction (DM) of A. oxyphylla, which are rich in phenolic compounds, against CCl₄-induced hepatic injury in vitro and in vivo. EE, DM and silymarin ameliorated CCl₄-induced decrease of cell viability and increase of reactive oxygen species (ROS) in HepG2 cells. The CCl₄-induced changes of glutathione (GSH) and methane dicarboxylic aldehyde (MDA) levels, and the decrease of superoxide dismutase (SOD) and catalase (CAT) activities were all restored with the pretreatment of EE, DM and silymarin. The results in liver injury model in rats showed that EE, DM and silymarin could significant decrease the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin than the model group. Liver histopathology revealed that EE and DM attenuated the incidence of liver lesions triggered by CCl₄ intoxication. They also effectively relieved CCl₄-induced oxidative damage. Western blot analysis indicated NF-E2-related factor (Nrf2) pathway played an critical role in the protection of EE and DM against CCl₄-induced oxidative stress. In conclusion, the extracts from A. oxyphylla might be used as hepatoprotective agents.