Unlike the previous report, which suggested that the AKT signaling pathway is associated with the downregulation of HNF4α in rat primary hepatocyte [14], our results here reveal that the suppression of HNF4α during long-term HBV infection is associated with the ERK signaling pathway in human hepatoma cell lines and mouse models. The gene discussed is HNF4A; the disease is hepatocellular carcinoma.