BACKGROUND: Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide. While traditional prognostic factors have mainly focused on tumor characteristics, recent evidence underscores the importance of immune response, inflammation, and nutritional status in determining patient outcomes. This study assesses the prognostic value of prognostic immune-inflammatory-nutritional (PIIN) score in predicting overall survival (OS) of NSCLC patients. METHODS: A retrospective analysis was conducted on the clinical data of 406 NSCLC patients who underwent surgical treatment. The optimal PIIN score cut-off value was established using receiver operating characteristic (ROC) curve analysis, dividing patients into high and low PIIN score groups. Both univariate and multivariate Cox regression analyses identified independent prognostic factors, which were used to construct a nomogram. RESULTS: The ideal PIIN score cut-off value was 24.2. Multivariate Cox regression analysis demonstrated that PIIN score [hazard ratio (HR): 2.116, 95% confidence interval (CI): 1.305-3.430, P=0.002], tumor-node-metastasis (TNM) stage (stage II: HR: 2.437, 95% CI: 1.223-4.855, P=0.01; stage III: HR: 6.753, 95% CI: 3.779-12.065, P<0.001), and forced expiratory volume in the first second (FEV) (HR: 2.335, 95% CI: 1.402-3.889, P=0.001) were independent prognostic factors. The concordance index (C-index) of the nomogram constructed based on independent risk factors was 0.838 (95% CI: 0.736-0.906). ROC analysis showed that the area under the curve (AUC) values for the nomogram's prediction of 1-, 3-, and 5-year OS were 0.843, 0.831, and 0.825, respectively. CONCLUSIONS: PIIN score was validated as an independent and reliable predictor of OS in stage I-III NSCLC patients after surgery. This score provides a valuable tool for individualized prognosis evaluation in clinical practice.