We also present evidence that SHP2 links HBx–NF-κB with EGFR signaling-mediated hepatocyte proliferation and that the HBx–NF-κB–SHP2 and IL-6–JAK–STAT3 pathways were active in parallel at an early stage of HCC development; accordingly, losses of activity in these pathways could accelerate HCC development. Here, STAT3 is linked to hepatocellular carcinoma.