Increased mROS damages mitochondrial DNA (mtDNA) that might play a role in hepatocellular carcinoma (HCC), and HBx-mediated ROS generation activates transcription factors such as Foxo-4 in Chang cells stably expressing HBx (Chang-HBx) and in primary hepatic tissues from HBx-transgenic mice; STAT-3, as well as NF-κB in HBx-transfected HepG2 cells [27,35,36,37]. This evidence concerns the gene FOXO4 and hepatocellular carcinoma.