Objective To Investigate the effect of copper ions on the radiosensitivity of nasopharyngeal carcinoma(NPC)and identify potential targets to improve the efficacy of NPC radiation therapy.Methods The content of copper ions in normal nasopharyngeal epithelial cell line NP69 and a variety of NPC cell lines was detected by a copper microplate assay.After adding 0,5,10,20,50,100,200 μmol/L copper ion solution and 0,0.05,0.1,0.2,0.5,1.0,2.0 mmol/L TEPA solution,CCK-8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation.And determine the drug concentration to be used in subsequent experiments.CCK-8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation,and to determine the drug concentration used in the copper ion group and TEPA group in the subsequent experiments.CCK-8 assay and clone formation assay were used to detect the changes in radiosensitivity of NPC cells after drug treatment.The DNA damage and MAPK-ERK signaling pathway-related protein expression of NPC cells in each group before and after irradiation were detected by Western blot.Results The content of copper ions in NPC cells was significantly higher than that in normal naso-pharyngeal epithelial cells(P＜0.05).When the concentration of copper ion solution was lower than 50 μmol/L,the radiation resistance of CNE1 cells was improved,and the radiation sensitivity of SUNE1 cells was increased by 0.1～0.2 mmol/L TEPA(P＜0.05).Compared with the control group,the NPC cell radiotherapy resistance of copper ion group was enhanced,and the NPC cell radiotherapy sensitivity of copper ion group was enhanced(P＜0.05).Compared with the control group,the activation degree of MAPK-ERK pathway in copper ion group was up-regulated(P＜0.05).MAPK-ERK pathway inhibitor SCH772984 effectively reversed copper-mediated NPC radiotherapy resistance(P＜0.05).Conclusion The increased copper ion content in NPC cells promoted the radiotherapy resistance of NPC cells by activating the MAPK-ERK signaling pathway.