Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protective effect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were divided into five groups (n=10, each). The control group received a single dose of normal saline, the diethylnitrosamine (DENA) group received a single intra-peritoneal dose at 200mg/kg body weight, and the 3rd, 4th and 5th groups were given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300,200 and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alpha feto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), serum liver enzymes (AST, ALT, ALP and GGT) levels as well the activities and gene expression of glutathione peroxidise (GPx), glutathione reductase (GR), catalase (CAT) and super oxide dismutase (SOD). Curcumin significantly lowered the serum levels of AFP, IL-2 and IL-6, ALT, ALT, and malondialdehyde (MDA) as well gene expression of IL-2 and IL-6. In contrast it increased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR against DEN-induced hepatocarcinogenesis in albino rats was proven.