The heterogeneity of hepatocellular carcinoma (HCC) has become a scientific problem, which must be solved urgently. Formerly, HCC prevention mainly focused on the HCC cells themselves but in recent years, HCC prevention based on the HCC microenvironment is the new strategy. Focusing on the liver regeneration microenvironment of HCC rather than just HCC cells may be a breakthrough in the study of HCC tumor heterogeneity and the prevention and treatment of HCC.