This study aimed to explore the relationship between the comprehensive nutritional index (CNI) and quality of life in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiation therapy (IMRT). The nutritional index, which includes total lymphocyte count, hemoglobin and albumin levels, body mass index, and usual body weight percentage, was evaluated pre-treatment and post-treatment in patients who underwent IMRT. The quality of life of NPC patients was measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H& N35) at four time points: pretreatment, post-treatment, and 3 and 6 mo after IMRT. A comprehensive nutritional model was used to assess the correlation with QLQ-H& N35. The nutritional index decreased significantly post-treatment. The CNI was associated with immunotherapy; the International Union Against Cancer (UICC) stage; concurrent chemotherapy; speech problems, trouble with social contact, feeling ill and having dental problems at pre-treatment; sexuality at 3 mos post-treatment; and sensory problems and xerostomia at 6 mo post-treatment (P < 0.05). The nutritional status and QLQ-H& N35 scores in NPC patients decreased during IMRT. Our study provides an alternative measure of the CNI to improve the QLQ-H& N35 evaluation system for patients with NPC.