Curcumin medicinal applications are hindered by its well-known unstable metabolic state and also insufficient absorption and bioavailability.In recent years, nano-based drug delivery system has effectively improved the aqueous solubility and bioavailability of curcumin. The current study was established to evaluate the protective and therapeutic effect of nano-curcumin (Nano-Cur) in hepatocellular carcinoma induced in rats. Fifty white albino rats were divided into 5 groups 10 rat of each. Group I served as negative control while group II received DEN with a daily dosage of (20 mg/kg body weight) orally by gavage during twelve weeks. Group III rats received Nano-Cur (20 mg/kg body weight) three days a week by gavage for eighteen weeks. Group IV rats received DEN as group II and treated with Nano-Cur as group III for six weeks. Group V received Nano-Cur as protector, for six weeks before DEN administration with continuous administration with Nano-Cur till the experiment end. Blood and tissue samples were collected and removed for determination of biochemical, antioxidant, cytokine and apoptotic marker p53 examination at the end of experiment. Based on the findings, DEN group indicated significantly increased serum liver function enzymes ALT, AST, ALP this was accompanied with significant decrease in liver antioxidant enzyme activities of (SOD and CAT) along with significant elevation in lipid peroxidation. DEN significantly elevated IL-6 and reduced apoptotic marker p53. The findings of this research indicated that Nano-cur has a anemaelioration effect against DEN carcinogenic effect.