Resveratrol is a polyphenolic compound found in wine, which is mainly produced by the grapevine and exerts chemopreventive effects against hepatocellular carcinoma. However, the underlying molecular mechanisms have remained to be fully elucidated. The present study assessed whether resveratrol-induced apoptosis was mediated via the activation of the forkhead box O3a (FoxO3a) transcription factor. It was demonstrated that resveratrol treatment induced apoptosis in HepG2 cells, and that this pro-apoptotic effect was accompanied with increases in the expression of apoptotic protein Bim. Following resveratrol treatment, Akt-mediated phosphorylation of FoxO3a was observed to be diminished in HepG2 cells. Furthermore, resveratrol enhanced the nuclear levels of FoxO3a and mediated neuronal death via Bim. The present study demonstrated that resveratrol induced apoptosis in HepG2 cells through activation of the transcription factor FoxO3a and increasing the expression of Bim protein.