To investigate the protective effect of Emblica Total Phenolic Acids (ETPA) on acute liver injury in mice and its possible mechanism. Mouse model of acute liver injury was established, which was induced by Acetaminophen (APAP). The mice were divided into normal group, model group and ETPA groups (15, 30 and 60 mg•kg-1). UV-Vis spectrophotometry was used to detect serum Alanine Aminotransferase (ALT) and Aspartate Amino Transferase (AST) activities of various groups, as well as Superoxide Dismutase (SOD) and Malonaldehyde (MDA) levels in liver homogenates. HE staining was performed to observe the pathological changes in liver. Compared to the model group, intragastric administration of ETPA (30 and 60 mg•kg-1) could significantly decrease the elevated activities of ALT and AST in serum. ETPA was also found to decrease the elevated MDA and SOD levels in liver homogenates. ETPA could significantly improve the degree and extent of hepatocellular necrosis and reduce inflammatory cell infiltration. ETPA has a protective effect on APAP-induced acute liver injury in mice, and relevant mechanism may be associated with its anti-oxidation effect.