PURPOSE: This study aimed to evaluate the prognostic value of the pre-treatment prognostic nutritional index (PNI) in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with endostar combined with concurrent chemoradiotherapy (ECCRT). METHODS: Clinical data from 92 patients with LANPC who underwent ECCRT between May 2015 and December 2020 were retrospectively analyzed. The PNI was calculated using peripheral blood samples taken 1 week before treatment. The optimal cut-off value for PNI was determined via receiver operating characteristic (ROC) curve analysis based on overall survival (OS). Patients were categorized into high PNI and low PNI groups. The Kaplan-Meier method assessed the impact of PNI on survival, while univariate and multivariate Cox regression analyses identified independent risk factors affecting patient survival. RESULTS: The optimal cut-off value of PNI was 50.05. The 3-year OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRRFS) rates were 91.07% vs. 75.00% (P = 0.002), 83.93% vs. 66.67% (P = 0.015), 89.29% vs. 69.44% (P = 0.004), and 94.64% vs. 91.67% (P = 0.668) in the high PNI and low PNI groups, respectively. A low PNI was associated with shorter OS (HR = 3.592, P = 0.004), PFS (HR = 2.890, P = 0.017), and DMFS (HR = 3.826, P = 0.008). Multivariate analysis revealed that PNI was an independent prognostic factor for OS, PFS, and DMFS. CONCLUSIONS: The PNI may serve as a valuable prognostic predictor for patients with LANPC receiving ECCRT, aiding clinicians in selectively providing multimodal interventions to optimize survival outcomes.