Resveratrol, a natural product, has been revealed to exert antitumor effects in multiple types of tumors. However, the antitumor effects of resveratrol on hepatocellular carcinoma (HCC) and its potential underlying mechanisms have not yet been elucidated. The present study demonstrated that resveratrol inhibited viability, proliferation, invasion and migration of HCC cells significantly in a timeâ and doseâdependent manner, indicating that resveratrol exerted antitumor effects in HCC. Furthermore, relative expression of autophagyârelated proteins Beclin1 and LC3 II/I ratio was increased while p62 expression was decreased by resveratrol treatment doseâdependently. The LC3+ puncta formation, which represented autophagosome formation was also markedly doseâdependently upregulated by resveratrol treatment, suggesting that resveratrol induced autophagy in HCC cells. In addition, treatment with autophagy inhibitor 3âmethyladenine (3âMA) counteracted the inhibitory effect of resveratrol on HCC cell proliferation, invasion and migration, indicating that suppressing autophagy may hamper the antitumor effect of resveratrol in HCC. It was revealed that resveratrol upregulated the expression of p53 while decreasing the ratio of phosphorylated protein kinase B (pâAkt)/Akt in HCC cells. Treatment with p53 inhibitor pifithrinâα and Akt activator insulinâlike growth factorâ1 decreased the expression of Beclin1 while significantly promoting cell proliferation, invasion and migration compared with the resveratrol treatment group. Taken together, the results of the present study revealed that resveratrol inhibited the proliferation and mobility of HCC cells through inducing autophagy via activating p53 and inhibiting phosphoinositide 3âkinase/Akt. Enhancing autophagy can augment the antitumor effects of resveratrol in HCC. Therefore, combining resveratrol with an autophagy inducer may be a viable option for treating HCC.