Objective: To investigate the role of CTLA-4, PD-1(programmed death-1), and PD-L1(programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups.Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1rs4143815 SNP and the long clinical benefit group showed a statistically significant association (p= 0.02). The nonresponder cohort displayed distinctive PD-L1haplotype (p= 0.05).Conclusion: PD-L1SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.