OBJECTIVE: This article aims to longitudinally compare nasopharyngeal carcinoma (NPC) patients' quality of life (QoL) during radiotherapy (RT) and identify QoL correlates. METHODS: This study included 98 patients, with 85 completing full follow-up. Data were collected at baseline (T), midpoint of RT (T), and RT completion (T), between October 2021 and November 2022. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RIOM severity was evaluated by the toxicity criteria of Radiation Therapy Oncology Group (RTOG). The nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS 2002), body mass index (BMI), and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalized estimating equation described the QoL evolution and correlated it with RIOM, nutritional status, and other influential factors. RESULTS: Significant deterioration was observed in various subscales of EORTC QLQ-C30 during RT, including global health status (GHS), physical function, role function, emotional function, fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation (all  ​< ​0.05). Substantial deterioration was also observed in RIOM, nutritional status, and part of hematological indexes (all  ​< ​0.05). The decline of QoL was associated with gender, age, education level, chemotherapy regimen, Karnofsky performance status (KPS) score, RIOM severity, NRS 2002 score, PG-SGA score, and lymphocyte level (all  ​< ​0.05). CONCLUSIONS: QoL declined during RT and were associated with certain factors. Healthcare professionals should focus on alleviating treatment-related complications and identifying individuals at high risk of malnutrition early to improve outcomes for patients with NPC.