Immunotherapy is revolutionizing the management of advanced non-small cell lung cancer (NSCLC). However, sustained responses are observed in only a minority of patients. Reliable biomarkers are required to identify potential beneficiaries. Interferon regulatory factor 4 (IRF4) plays a crucial role in immune regulation, suggesting its potential as a prognostic biomarker in NSCLC immunotherapy. This study aimed to investigate the predictive role of IRF4 expression in patients with NSCLC receiving immunotherapy.