On the other hand, under the condition of hypoxia caused by the rapid growth of HCC, HMGB1 was translocated from the nucleus to the cytosol and bound mitochondrial DNA (mtDNA) in the cytoplasm of hypoxic tumor cells, inducing tumor growth by activating TLR-9 signaling pathways both in vitro and in vivo [53]. This evidence concerns the gene HMGB1 and hepatocellular carcinoma.