Nanomaterials-based drug delivery systems display potent applications in cancer therapy. We synthesized a novel anticancer drug, nano-gold loaded with resveratrol (Res-GNPs), which were characterized using UV-Prove, zetasizer and transmission electron microscope. MTT assay, flow cytometry, TUNEL, immunohistochemistry and western blot analysis were performed to explore the antitumor activity of Res-GNPs in liver cancer cells and tumor xenografts. Res-GNPs showed a stronger effect on inhibiting cell proliferation and promoting apoptosis in Hepg2 cells than that of free Res. Res-GNPs induced apoptosis in Hepg2 cells by down-regulating pro-caspase-9, pro-caspase-3, PI3K and Akt and upregulating caspase-8 and bax. In xenograft studies, Res-GNPs remarkably suppressed tumor growth, promoted tumor apoptosis and decreased the expression of vascular endothelial growth factor (VEGF) in tumor tissue. Furthermore, HE staining showed that no observable toxicity was found in heart, liver, kidney and spleen. The datum confirmed that Res-GNPs possess better antitumor effect than Res in vitro and in vivo, which may be due to gold nanoparticles carry more resveratrol into cells and locate in mitochondria. These results suggested that Res-GNPs possess significantly better anti-cancer effect than Res alone in vitro and in vivo, which may be helpful for the clinical therapy of liver cancer.