In the present study, we investigated the characteristics of HCC development in liver-specific Irs1-knockout (LIrs1KO) and liver-specific Irs2-knockout (LIrs2KO) mice treated with diethylnitrosamine (DEN), to understand the specific roles of Irs1 and Irs2 in hepatocarcinogenesis. The gene discussed is IRS2; the disease is hepatocellular carcinoma.