Curcumin is a conventional Chinese medicine, which exerts a marked effect on various tumor types and suppresses tumor invasion. The present study analyzed the antineoplastic effects of curcumin on human nasopharyngeal carcinoma (NPC) cells and determined the effects of endoplasmic reticulum (ER) stress on curcumin‑induced cytotoxicity. The Cell Counting Kit‑8 assay examined the viability of SUNE1 and SUNE2 NPC cells. The Annexin V/propidium iodide staining technique was used to detect cell apoptosis and flow cytometry was used to examine cell cycle distribution. Western blotting and immunofluorescence were used to detect ER stress‑associated molecules. Furthermore, the toxic effects of curcumin treatment alongside glucose‑regulated protein 78 (GRP78) knockdown using small interfering (si)RNA, and treatment with the pan‑caspase inhibitor Z‑VAD‑FMK and the protein kinase B (AKT) inhibitor MK‑2206 were detected. The results demonstrated that curcumin markedly reduced cell viability, blocked cell cycle progression and induced apoptosis of human NPC cells. In addition, curcumin activated ER stress‑associated proteins to participate in the apoptosis of human NPC cells. siRNA‑induced knockdown of GRP78 may be able to strengthen the toxic effects of curcumin through mediating the AKT signaling pathway. These findings indicated that downregulation of GRP78 promoted the therapeutic effects of curcumin on NPC cells. The present study identified a potential, novel therapeutic method for the treatment of NPC.