The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation.The portal system plays a crucial role in the dual blood supply to the liver,making it a significant factor in hepatic function.Several surgical strategies,such as portal vein ligation,associating liver partition and portal vein ligation for staged hepatectomy,and dual vein embolization,have high-lighted the portal system's importance in liver regeneration.Following hepatectomy or liver trans-plantation,the hemodynamic properties of the portal system change dramatically,triggering regeneration via shear stress and the induction of hypoxia.However,excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes.Furthermore,as the importance of the gut-liver axis has gradually been revealed,the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged.From these perspectives,this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.