Taken together, our results have demonstrated that HMGB1 promotes the proliferation and migration of HSCs via TLR4-dependent signal pathways of JNK and PI3K/Akt, which indicates a significant functional role of HMGB1 in the development of liver fibrosis and HMGB1 may be an effective target to treat liver fibrosis. This evidence concerns the gene AKT1 and Hepatic fibrosis.