In this study, we, for the first time, found that NS4B and HCV induced the expression of four cancer-related NF-κB target genes, C-myc, Mcl-1, Cyclin D1 and MMP-9 by the EOR-Ca2+-ROS-NF-κB pathway in both human hepatoma cells and primary human hepatocytes. The gene discussed is CCND1; the disease is hepatocellular carcinoma.