Objective We investigated the effects of curcumin on the Kelch-like ECH-associated protein-1 (Keap1) / antioxident responseelement (ARE) signaling pathway and on bile acid hepatointestinal circulation in hepatoma model mice. Methods C57BL/6 mice were randomly divided into control group, model group, a low dose ( 10 μg/g) curcumin group, a medium dose (20 μg/g) curcumin group, a high dose (30 μg/g) curcumin group, and a cisplatin (10 μg/g) group, with 12 mice in each group. except for the control group, the other groups were given diethylnitrosamine to induce the establishment of liver cancer models, After grouping, the pathological morphology of liver tissue was detected by hematoxylin eosin (HE). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and total bile acid ( TBA) serum contents of the mice were measured. The levels of serum interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) of mice were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of the Keap1/ARE pathway related proteins, Keap1 and nuclear factor erythroid 2 related factor 2 (Nrf2), were detected by quantitative real-time polymerase chain reaction (qRT-PCR) fluorescence analysis and Western blot. Results Compared with the control group, the liver tissue of mice in the model group showed canceration and other pathological damage. The levels of serum ALT, AST, TB, TBA, IL-6, TGF-β1, and Keap1 mRNA and protein in liver tissues were significantly increased (P <0. 05), and the levels of Nrf2 mRNA and protein were significantly decreased (P <0. 05). Compared with the model group, the liver tissue pathological damage of mice in the low, middle and high dose curcumin groups, and in cisplatin group was alleviated; the levels of serum ALT, AST, TB, TBA, IL-6, TGF-β1, and Keap1 mRNA and protein in liver tissue were decreased; and the levels of Nrf2 mRNA and protein were increased, with each index changing in a gradient fashion with the increase of curcumin dose (P <0. 05). There was no significant difference between the high dose curcumin group and the cisplatin group of mice (P >0. 05). Conclusions Curcumin can reduce liver damage and improve the circulation of bile acid in the liver and intestine. This may be achieved by the down-regulation of the expression of Keap1 and the activation of downstream ARE signals.