The purpose of this study was to investigate the significance of the Prognostic Nutritional Index (PNI) in predicting prognoses and guiding treatment choices of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). The 539 patients with newly diagnosed non-metastatic NPC were retrospectively analysed. The PNI was calculated as 10 x serum albumin (g/dL) + 0.005 x total lymphocyte count (per mm(3)). All patients were split randomly into a training set and a testing set. Receiver operating characteristic (ROC) curves were used to identify the cut-off value of PNI and test its prognostic validity. Survival curves were calculated by Kaplan-Meier method, and differences were compared with log-rank test. The median follow-up time was 109.5 months. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) of the whole cohort were 90.6, 85.8, 85.3 and 82.7%, respectively. The PNI cut-off value was 52.0 in the training set, which was significant in predicting DMFS, DSS and OS in the testing set. According to the PNI cut-off value, 220 patients of II-IVb stage treated by concurrent chemoradiotherapy (CCRT) were classified into PNI 52.0 and > 52.0 groups and the 5-year LRRFS, DMFS, DSS, and OS of PNI 52.0 group were significantly worse than the PNI > 52.0 group. Our results suggest that the PNI is a reliable independent prognostic factor in NPC patients treated with IMRT. For stage II-IVb patients with PNI 52.0, CCRT alone does not achieve satisfactory outcomes, and further studies on treatment optimization are needed.