Moreover, we found that hepatitis B virus X protein can induce the translocation and secretion of HMGB1 to promote the malignant progression of HCC in an autocrine/paracrine manner, and HMGB1 released by tumor cells plays a critical role in TLR4-dependent activation of platelets which in turn promotes HCC metastasis14,15. Here, HMGB1 is linked to hepatocellular carcinoma.