Objective：This study aims to ohserve the protective effect of human-TLR4 IgG2（hTLR4 IgG2）on acetaminophen（APAP） induced liver injury，and to investigate the protective mechanism of hTLR4 IgG2 in drug induced liver injury. Methods：The hTLR4 Fab plasmid in our laboratory were used as templates to amplify the variable region genes，and the hTLR4 IgG2 eukaryotic expression vector was constructed and transfected into CHO-S cells. The stable transfectants strains and culture supernatants were collected. Finally，hTLR4 IgG2 was purifieded using a protein G column. Total 18 C57BL/6J mice were randomly divided into three groups：saline group，APAP（600 mg/kg）and the APAP+hTLR4 IgG2（5 mg/kg）group. The survival rate of mice after 24 hours intraperitoneal injection with APAP was compared. Repeat the above experimental grouping and modeling methods were repeated. Aspartate transaminase（AST），alanine aminotransferase（ALT），interleukin-1（IL-1），interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in serum were also qualified，the liver was taken for pathological section and the expression of hepatic apoptosis protein was analyzed by Western blot after 8 hours intraperitoneal injection with APAP. Results：The hTLR4 IgG2 was successfully constructed and purified，and the results of ELISA showed that the antibody titer was 1∶204 800. Compared with the APAP group，the 24-hour survival rate of mice in the APAP+hTLR4 IgG2 group was significantly increased（P < 0.05）；the expression levels of AST，ALT and inflammatory cytokines in serum were significantly decreased（P < 0.05）；pathological detection results showed that the inflammatory cell infiltration，hyperemia and necrosis of liver tissue were significantly improved in APAP+hTLR4 IgG2 group，and the expression of apoptotic protein was decreased in the APAP+hTLR4 IgG2 group by Western blot. Conclusion：hTLR4 IgG2 can effectively inhibit the expression of inflammatory factors and apoptosis，and protect liver against APAP-induced injury in mice.