Previously, we reported that hypermethylation of the APC, CDKN2A, RASSF1A, HIC-1, GSTP1, RUNX3, SOCS1, and PRDM2 genes is a frequent event, even in early HCC [33], suggesting that hypermethylation of these TSGs could play a role in the early stage of hepatocarcinogenesis, and is independent of metastatic potential acquisition. This evidence concerns the gene HIC1 and hepatocellular carcinoma.