An increased ratio of KLF6SV1/wt KLF6 is present in a subset (6/33, 18%) of the HBV-related HCCs compared to matched ST. Reconstituting KLF6 in HepG2 cells by retroviral infection decreased proliferation and related markers including cyclin D1 and beta-catenin, increased cellular differentiation based on induction of albumin, E-cadherin, and decreased alpha fetoprotein.