Remarkably, several groups have shown that genetic ablation of classic oncoproteins such as inhibitor kappa-B kinaseβ (Ikkβ), inhibitor kappa-B kinaseβ 1/2 (Jnk1/2), epidermal growth factor receptor (EGFR), β-catenin, and protein kinase B (Akt) in hepatocytes exacerbated HCC developed spontaneously or induced by chemical carcinogen diethylnitrosamine (DEN),5, 6, 7, 8, 9 disclosing complex mechanisms of liver tumorigenesis. The gene discussed is IKBKB; the disease is hepatocellular carcinoma.