Purpose <p>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).</p> Methods <p>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&#xa0;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.</p> Results <p>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% (<i>P</i> = 0.002), 83.93% vs. 66.67% (<i>P</i> = 0.015), 89.29% vs. 69.44% (<i>P</i> = 0.004), and 94.64% vs. 91.67% (<i>P</i> = 0.668) in the high PNI and low PNI groups, respectively. A low PNI was associated with shorter OS (HR = 3.592, <i>P</i> = 0.004), PFS (HR = 2.890, <i>P</i> = 0.017), and DMFS (HR = 3.826, <i>P</i> = 0.008). Multivariate analysis revealed that PNI was an independent prognostic factor for OS, PFS, and DMFS.</p> Conclusions <p>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.</p>