ObjectiveTo develop and validate a Nomogram for predicting severe immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy based on clinical features and inflammatory indicators. MethodsA total of 423 patients with advanced NSCLC treated with immunotherapy between January 2023 and January 2025 at Tianjin Fourth Center Hospital and Tianjin Cancer Hospital Airport Hospital were enrolled. Patients were divided into a severe irAEs group (≥grade 3, n=76) and a non-severe irAEs group (n=347), then randomly allocated into training and validation cohorts (7:3 ratio) . Clinical data, neutrophil-to-lymphocyte ratio (NLR), and interleukin-6/C-reactive protein (IL-6/CRP) levels were collected. Independent risk factors for severe irAEs during immunotherapy in advanced NSCLC were identified through logistic regression analysis, and a nomogram model was constructed accordingly. The discriminative ability, accuracy, and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). ResultsAmong the 423 included patients [274 males, 149 females, aged 44-78 (60.77±5.91) years], the overall incidence of irAEs was 57.92% (245/423), with severe irAEs occurring in 17.97% (76/423). Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance score ≥2, programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) ≥50%], combination therapy regimen, low NLR values, and high IL-6/CRP ratio were independent risk factors for severe irAEs during immunotherapy in advanced NSCLC (P<0.05). The area under the ROC curve (AUC) was 0.948 [95%CI (0.912, 0.985)] in the training cohort and 0.946 [95%CI (0.917, 0.976)] in the validation cohort. Calibration curves and DCA demonstrated good consistency and clinical net benefit of the model. ConclusionThe nomogram integrating clinical features and inflammatory markers effectively predicts the risk of severe irAEs in advanced NSCLC patients receiving immunotherapy, exhibiting excellent discrimination, calibration, and clinical practicality.