Objective To explore the protective effect and its mechanism of B7-H4 on the immuno hepatic injury. Methods The immuno hepatic injury was induced by Concanavalin A (Con A). Sixty KM mice were randomly divided into 4 groups with 15 mice in each group: Group A (saline), Group B (pcDNA3.1-mB7-H4-Fc), Group C (pcDNA3.1), Group D (Con A). One day before the injection of Con A (25 mg/kg), the mice in Group B and Group C received the injection of 100 μg pcDNA3.1-mB7-H4-Fc and 100 μg pcDNA3.1 respectively. The blood samples were collected at 12 h, 24 h and 48 h after Con A injection, the levels of ALT, AST, IL-4 and IFN-γ were measured. Five mice in each group were sacrificed at the above 3 time points, the liver tissue were harvested for histopathological detection. Results After Con A injection, the level of ALT in Group B,C, and D were higher than that in Group A. The level of ALT in Group B was lower than that in Group C and D. The significant difference was found between Group B and Group C. The hepatic injury of Group B was less serious than that of Group C and D. Conclusion B7-H4 may have protection on the immune injury of liver induced by Con A.