Objective To investigate the effect of EphA2 protein on the chemosensitivity of paclitaxel in nasopharyngeal carcinoma (NPC) in vitro. Methods NPC 58F cells were transfected with EphA2 overexpression vector pEGFPN1EphA2 and empty vector pEGFPN1 by LipofectAMINE 2000 and Western blot was used for detecting the transfection efficiency. The IC50 values of paclitaxel in each group were obtained by CCK8 assays. Changes of cell cycle and apoptosis of 58F cells were examined with fluorescenceactivated cell sorting analysis. Results Compared with parental 58F cells (1.40±0.05) nM/L and 58F cells transfected with empty vector (1.30±0.06) nM/L, the IC50 value of paclitaxel was significantly upregulated in 58F cells transfected with EphA2 overexpression vector (3.80±0.52) nM/L (P<0.05). Meantime, cells in G0/G1 phase were greatly decreased ［(45.76±3.89)% vs (65.85±2.28)%, (45.76±3.89)% vs (64.52±3.31)%］, but cells in S phase ［(31.56±1.59)% vs (25.76±1.89)%, (31.56±1.59)% vs (24.55±3.64)%)］ and G2/M phase ［(23.10±4.55)% vs (8.39±0.81)%, (23.10±4.55)% vs (10.94±3.27%)］ were obviously increased (P<0.05). However, no significant difference was found in cell apoptosis rate among the 58F cells of the three groups (P>0.05). Conclusion EphA2 can regulate the chemosensitivity of paclitaxel via influencing the cell cycle in NPC cells.