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The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells. Following resveratrol treatment, U937 and MOLT-4 markedly increased the population of late apoptotic cells but MCF-7 and HepG2 underwent apoptosis with an increased population of early apoptosis, and resveratrol-induced DNA fragmentation was observed only in leukemic cells. Activation of sirtuin 1 and adenosine-monophosphate-activated protein kinase was not responsible for resveratrol-induced cancer cell death. Instead, resveratrol significantly reduced Akt activation with the downregulation of H-Ras, resulting in facilitation of Bax translocation to mitochondria in leukemic cells. This study suggests that resveratrol can induce apoptotic cell death in human leukemic cells to a greater extent than in human solid tumor cells via reducing Akt activation due to Ras downregulation.