Hepatocellular carcinoma is the most common primary cancer of the liver. The objective of this study was to evaluate the effects of resveratrol and quercetin alone or in combination against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DENA) and phenobarbital (PB) in rats. One hundred and twenty five adult male albino rats were employed in this work which was included in two experiments. In the first, thirty one rats were injected (i.p) with saline solution (control group).  The HCC rats group (94 rats) was injected i.p with a single dose of DENA once/week for 3 weeks.  After 3 weeks, rats were promoted by i.p injection of PB once a day for 7 days. After the induction period, 10 rats from each of the previous group were taken to compare the alterations in the biochemical and physiological parameters. In the second experiment, four comparisons were made between 21 normal control rats and 84 HCC rats. The HCC rats were divided into the following subgroups; (1) HCC rats left without any further treatment and served as a recovery group. (2) HCC rats received daily i.p resveratrol and served as a resveratrol group. (3) HCC rats treated with i.p injection of quercetin and served as a quercetin group. (4) HCC rats received mixture of resveratrol and quercetin for 2, 4 & 8 weeks and served as a resveratrol and quercetin group.    The obtained data revealed remarkable changes in all studied parameters of hepatocellular carcinoma rats than those in control ones. When HCC rats were treated with combined treatment of resveratrol and quercetin for 2, 4 & 8 weeks a considerable amelioration effects in all studied parameters were pronounced dependent on time of treatment and certain mechanisms which were discussed according to available recent researches.