Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells. Compared to control DMSO‑treated CNE-1 cells, resveratrol inhibited colony-forming ability and induced G1 phase cell cycle arrest. Radiation survival curves confirmed resveratrol significantly sensitized CNE-1 cells, and resveratrol in combination with 2 Gy irradiation synergistically increased apoptosis. Immunoblotting showed resveratrol dose- and time-dependently downregulated E2F1 and phospho-AKT (p-AKT). Knockdown of E2F1 significantly increased radiosensitivity and downregulated p-AKT; overexpression of E2F1 reversed resveratrol-induced radiosensitivity and upregulated p-AKT. In vivo, 50 mg/kg/day resveratrol and 4 Gy irradiation led to significantly lower tumor volume and tumor weight compared to resveratrol or irradiation alone. Our findings show that resveratrol increases the radiosensitivity of NPC cells by downregulating E2F1 and inhibiting p-AKT, and therefore has potential as a radiosensitizer for NPC.