Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protectiveeffect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were dividedinto 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 groupswere given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300,200and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alphafeto-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 itincreased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR againstDEN-induced hepatocarcinogenesis in albino rats was proven.