Hepatocellular carcinoma (HCC) has reported high prevalence rates recently in Egypt and worldwide. Livin is one of the apoptotic inhibitor genes and its silencing increases the apoptotic incidence and hence the resistance to cancer proliferation. Resveratrol (Res) and gold nanoparticles (Au-NPs) have been documented for their antitumor activities. Purpose: In the present study, we used hepatocarcinoma as a model to investigate the combination of Res and Au-NPs (Res-Au-NPs) antitumor activity, via their effect on the expression of livin' and A-fetoprotein genes (AFP). Methods: Au-NPs (size: 50.0±2.0 nm) were produced by the seeded growth technique. The HCC rat model was administered with Res, Au-NPs, and their combination for two months. Livin and AFP gene expressions, DNA damage, and pathological changes in the liver tissues were assessed. Results: Our results revealed a significant reduction in livin' and AFP mRNA expression levels in HCC rats treated with a combination of Res and Au-NPs compared to those treated with Res or Au-NPs alone. This reduction was accompanied by increased DNA damage in the same group. The histological examination revealed an improvement in parenchymal structure with decreased degenerated hepatocytes in the Res-Au-NPs treated group in comparison to HCC, Res, and Au-NPs groups. Conclusion: the combination of Res and Au-NPs might be more effective in HCC treatment than using Res or Au-NPs alone may be due to the synergetic effects of both, which might be a prospective directed approach for the treatment of HCC.