Moringa olifera was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of moringa olifera on Diethylnitrosamine (DEN) induced Hepatocellular carcinoma in rats. Fourty five male albino rats were divided into three groups. Group (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN then treated with moringa at a dose level of (500 mg/kg b.wt/orally) dissolved in distilled water for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis of liver tissue revealed significant upregulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with moringa olifera to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. These findings suggest the potential efficacy of moringa as an additional chemopreventive agent in treatment of hepatocellular carcionoma via initiation of tumor suppressor gene (P53) and modulating the metabolic activation of detoxification Enzyme (cytochrome P450 2E1) and antiinflammatory effect.