Compared with tumor-adjacent tissues, HCC tissues demonstrate more TIM-1+ Breg cell infiltration, probably because HCC produced exosomal HMGB1 can activate and promote the proliferation of TIM-1+ Breg cells via the Toll-like receptor 2/4 (TLR2/4)-MAPK pathway, and the TIM-1+ Breg cells express immunosuppressive IL-10 to strongly inhibit CD8+ T cell activity, contributing to immune surveillance escape of HCC cells. This evidence concerns the gene HMGB1 and hepatocellular carcinoma.