Curcumin is widely used traditionally as an old plant in traditional medicine,  this work was aimed to investigate its possible protective effect against chemically induced Hepatocellular carcinoma (HCC) in rats. Fifty male albino rats, weighing 120±20g each, were used. Rats were divided to five groups ( n=10) for each group, control group  received a single dose of normal saline, diethylnitrosamine (DENA) bearing non-treated group received a single intra-peritoneal dose of DENA (200mg/Kg body weight), the 3rd, 4th and 5th groups were DENA bearing treated group daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300,200 and 100 mg Kg-1 b.wt. respectively  for 20 weeks. Serum, and liver samples were used for determination of alpha feto-protein (AFP), Interleukine-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 was significantly lower the serum level of AFP, IL-2 and IL-6 , ALT, ALT malondialdehyd (MDA) level as well the level of  gene expression of IL-2 and IL-6 in contrast increase the levels of gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR against DEN-induced hepatocarcinogenesis in albino rats was proven.