AIM: To analyze the expression of secreted phosphoprotein 1 (SPP1) and programmed cell death-ligand 1 (PD-L1) in SMARCA4-deficient non-small cell lung cancer, and to provide a scientific basis for the study of the follow-up treatment of this rare pathological type of lung cancer. METHODS: The clinical and pathological characteristics of 12 patients with this disease were analyzed retrospectively, and the patients were divided into two groups of adenocarcinomas and poorly differentiated carcinomas according to their morphological characteristics, and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups. RESULTS: SPP1 expression was detected in all patients and Its expression level was significantly higher in the poorly differentiated carcinoma group compared with the adenocarcinoma group (P=0.015); PD-L1 expression was found in 6/7 patients (5 cases were not measured), compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carcinoma group (P=0.048) and the PD-L1 difference between the two groups suggested that the results were similar to those of SPP1. CONCLUSION: SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1. It was more pronounced in patients with poorly differentiated carcinoma. There may be a positive correlation between SPP1 and PD-L1 expression in SMARCA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies.