[Abstract] Objective: To explore the retrospective study of METTL3 combined with Programmed death cell ligand 1 (PD-L1) detection in predicting the therapeutic effect and prognosis of Programmed death cell protein 1 (PD-1) inhibitors in NSCLC patients. Methods: Primary lesion tissues from NSCLC patients were collected. IHC was used to detect the protein expression of PD-L1 and METTL3, and the association with the effect of PD-1 inhibitor treatment and prognosis in patients with NSCLC was analyzed. Results: A total of 228 cases were collected. Among them, the protein expression of METTL3 was related to the pathological type, Eastern American Oncology Collaborative Group (ECOG)score, therapeutic line, therapeutic effect and Response Evaluation Criteria in Solid Tumors (RECIST) factors. Patients with high METTL3 protein expression had a median Progression-free-survival (PFS) of 12.33 months, while those with low or no METTL3 protein expression had a median PFS of 6.50 months. In NSCLC patients treated with PD-1 antibody, high METTL3 protein expression was associated with better PFS. The median Overall-survival (OS) of patients with high METTL3 protein expression was 23.54 months, and that of patients with low or no METTL3 protein expression was 20.93 months. Patients with high METTL3 protein expression were associated with better OS. Conclusion: Detection of METTL3 protein expression level may be a new target for predicting the efficacy of PD-1inhibitors in patients with NSCLC.