Hepatocellular carcinoma (HCC) is one of the major health burdens and the fifth most common cancer worldwide. Although there are several drugs available to control cancer growth, there are fewer drugs presently available to specifically inhibit the metastasis of cancer cells or prevent its angiogenesis. The present study aimed to investigate the protective or therapeutic effect of resveratrol (natural phytoalexin) on diethylnitroseamine (DENA) induced hepatocarcinogenesis in rats. Rats were injected with a single dose DENA (200mg/kg b.w, i.p) only or with pre and post treatment of low and high doses of resveratrol (300mg/kg b.w and 450mg/kg b.w) respectively by feeding for 9 months. To elucidate the mechanism by which resveratrol exerts its function as anticancer agent, the following parameters were determined: aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), total bilirubin as liver function test; vascular endothelial growth factor (VEGF) as a marker for angiogenesis and heparanase, elastase and matrixmetalloproteinases(MMPs) as markers of metastasis. Histopathological investigation was also confirmed. All parameters are elevated in DENA group, which confirmed by histopathological analysis where hepatic hemorrhages associated with necrosis, hyperchromatism, hyperplasia, proliferating hepatocytes were noticed. While the administration of resveratrol improved all biochemical and histopathological changes in post-treated groups more than pre-treated one, indicating that resveratrol may be a potent anticancer agent and its therapeutic effect is more potent than protective effect.