Objective To explore the effects of comprehensive psychological nursing intervention on patients with nasopharyngeal carcinoma during radiotherapy, so as to provide references for alleviating their physical and mental pain and to improve their quality of life. Methods From July 2016 to April 2017, a total of 124 cases of nasopharyngeal carcinoma patients treated by radiotherapy from a ClassⅢGrade A hospital were recruited in the research, of which 63 cases from July to December 2016 were assigned as control group and 61 cases from January to April 2017 were assigned as intervention group. Routine nursing care was provided in the control group. On the basis of the routine nursing, individual combined with group intervention was applied in the intervention group according to the psychological and behavioral interventions before and during radiotherapy. The nursing intervention lasted from the beginning of the first radiotherapy till the end of the therapy course in both groups. By the end of the therapy, all the patients were investigated with Distress Thermometer (DT) and the short Quality of Life Scale for Nasopharyngeal Carcinoma with 13 items (QOL-NPC13). Results The scores of DT in the control group and the intervention group were (8.08±0.58) and (5.30±1.11) respectively, and the difference was statistically significant (t=19.316,P<0.001). The scores of body function, psychological spirit, social relationship, toxic side effect and the quality of life of the intervention group were all higher than those of the control group, the differences were statistically significant (Z=-4.674,-7.894,-4.755,-4.842,-8.114; P< 0.001). Conclusions Comprehensive psychological nursing intervention is helpful to relieve the psychological pain and improve the quality of life in patients with nasopharyngeal carcinoma undergoing radiotherapy.