This investigation examined the relationship between hepatocellular cancer and diabetes and obesity. Twenty-eight male rats at age 2-3months were used in this study, were divided into 5 groups: G1 control negative fed normal feed, G2 Fed concentrated feed till obesity, G3 STZ was given once at 70 mg/kg B.W for the induction of DM and fed normal feed and G4 STZ was given once at 70 mg/kg B.W for the induction of DM and fed concentrated feed. Blood was aspirated weekly for serum separation. The glucose and liver function tests were done at 0,3,6,12 weeks of the study. Livers were collected from rats at end of experiment for histopathology and immunohistochemical detection of GS expression in hepatocytes. The current results showed that glucose levels increase significantly (p≤0.05) in G3 and G4 as compared with control group, while G2 showed increase in glucose levels with the time advanced. The levels of both AST and ALT were increased significantly in G3 and G4 when compared with G1, while G2 showed increasing both parameters with days advancement. One rat from G2 showed HCC, while G3 showed that 3 animals were have HCC and G4 showed that 4 animals with HCC. These liver tumors histologically resembled human HCC in terms of portal invasion and severe nuclear and structural atypia. Groups of liver tumors all responded well to the recognized human HCC marker GS. In conclusion, the results of this research provide support to the hypothesis that diabetes and obesity both have a role in elevating the risk of HCC.