The interaction of extracellular HMGB1 with its receptors RAGE/TLRs on cell surface may activate intracellular NF-κB pathways, inducing the elevation of leukocyte adhesion molecules and proinflammatory cytokines, thereby promoting inflammation and creating a sustained tumor microenvironment, and ultimately resulting in HCC [33]. Here, HMGB1 is linked to hepatocellular carcinoma.