This study was designed to investigate the role of (Curcumin/ Copper / cetyltrimethylammonium bromide) nano particles complex against hepatocellular carcinoma (HCC) induced in rats. Forty rats were divided into four groups. Group 1(negative control group): normal rats. Group 2 (Diethylnitrosamine) (DEN): rats administrated orally DEN with a dose of 20 mg/kg b. wt., five times a week / 6 weeks for HCC induction. Group 3 (protective ): rats were orally treated with Curcumin/ CU / CTAB (dissolved in Tween-80 (1 %) in 0.9 % normal saline) at a dose of 35 mg/kg b. wt., five times a week / 15 weeks as 2 weeks before DEN then, during administration of DEN and 15 weeks after DEN administration. Group 4 )treated group) rats treated with Curcumin/ CU/ CTAB dissolved in Tween-80 (1 %) in 0.9 % normal saline), at a dose of 35 mg/kg b. wt., five times a week / 15 weeks, following the administration of DEN for 6 weeks . Injection of DEN induced a significant increase in serum level of alpha-fetoprotein (AFP), alpha-L-fucosidase activity (AFU) and vascular endothelial growth factor (VEGF). On other hand, marked depletion in tissue antioxidants including superoxide dismutase (SOD), glutathione perioxidase (GPX) activities, and reduced glutathione (GSH) concentration. Administration of (Curcumin/ CU/ CTAB) nano composite was able to prevent cellular damage induced by reactive oxygen species (ROS) and able to make changes of tumor markers and tissue antioxidants nearly toward control.