Previous studies have reported that cytoplasmic translocation and secretion of HMGB1, as well as phosphorylation of NF-κB p65, were markedly upregulated in mouse livers following chronic diethyl nitrosamine (DEN) or carbon tetrachloride (CCl4) treatment 13, 27, 28, we thus wondered whether the HMGB1-p-p65-KLF7-TLR4/PTK2 pathway was activated in the DEN/CCl4-induced HCC model. This evidence concerns the gene TLR4 and hepatocellular carcinoma.