Abstract: In order to investigate the protective effect and mechanism of curcumin（CUR） against acetaminophen（APAP）-induced hepatic injury in mice, in the experiment, sixty ICR mice were randomly divided into normal control group, model group, N-acetylcysteine group（150 mg/kg N-acetylcysteine by gavage of body weight）, curcumin low dose group（50 mg/kg CUR by gavage of body weight）, curcumin medium dose group（100 mg/kg by gavage of body weight）, and curcumin high dose group（200 mg/kg CUR by gavage of body weight）. After 10 d of continuous prophylactic gavage in the N-acetylcysteine group and in the curcumin low dose, medium dose, and high dose groups, acute liver injury was induced in mice by a single intraperitoneal injection of APAP（300 mg/kg） by weight; after 24 h, blood was collected from the eyeballs and the mice in each group were executed, and the liver index was calculated. The activities of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, lactate dehydrogenase（LDH） in sera and the contents of catalase（CAT）, superoxide dismutase（SOD） and glutathione（GSH）, malondialdehyde（MDA）, reactive oxygen species（ROS） in liver tissue were detected. And the liver tissue was taken for H.E. staining to observe the pathological and histological changes of mouse liver. The mRNA relative expression levels of Trx-1/TXNIP/NLRP3 pathway in the liver were detected by RT-qPCR. The results showed that compared with the normal control group, the hepatic index, serum ALT, AST, LDH and hepatic tissue MDA contents, and ROS level of the mice in the model group were significantly or very significantly higher（P＜0.05 or P＜0.01） in the model group; liver tissue GSH content and CAT and SOD activities were significantly or highly significantly decreased（P＜0.05 or P＜0.01）; Trx-1 mRNA relative expression was highly significantly decreased（P＜0.01）; mRNA relative expression of TXNIP, NLRP3, ASC, Caspase-1 and IL-1β was highly significantly increased（P＜0.01）. Compared with the model group, serum ALT, AST, LDH activity, liver index and liver tissue MDA and ROS contents of mice in curcumin low, medium and high dose groups were highly significantly reduced（P＜0.01）; liver tissue CAT, SOD activities and GSH content were significantly or highly significantly increased（P＜0.05 or P＜0.01）; mRNA relative expression of Trx-1 was significantly or highly significantly higher（P＜0.05 or P＜0.01）; mRNA relative expression of TXNIP, NLRP3, ASC, Caspase-1 and IL-1β was significantly or highly significantly lower（P＜ 0.05 or P＜0.01）. In the model group, the liver tissue was disorganized in the hepatic cord, with a large number of necrotic hepatocytes, nuclear lysis, and inflammatory infiltration and congestion of the hepatic sinusoids. Hepatic cord structure was basically normal and hepatocyte necrosis was reduced in all curcumin dose groups. The results suggested that curcumin exerted a protective effect on APAP-induced acute liver injury in mice through antioxidant and anti-inflammatory effect, and the mechanism might be related to the increase of Trx-1 expression and the decrease of TXNIP expression.