Abstract: Objective To analyze the changes in pulmonary function and clinical effectiveness of patients with stage Ⅲ and Ⅳ non-small cell lung cancer (NSCLC) after treatment with PD-1 inhibitor. Methods A total of 80 NSCLC patients who were treated in the Affiliated Hospital of Xuzhou Medical University from July 2019 to March 2021 were enrolled, and their clinical data were analyzed. Depending on different treatments, they were randomly divided into two groups:a control group (n=41) and an observation group (n=39).The control group received AP or TP chemotherapy, while the observation group underwent chemotherapy combined with PD-1 inhibitor. Both groups were subjected to first-line treatment. After four treatment cycles, both groups were compared for pulmonary function, T lymphocyte subsets (CD3⁺, CD4⁺, and CD8⁺), the levels of tumor markers in lung tumor and clinical effectiveness. Their toxic and side effects were also recorded. Results After treatment, the objective response rate (ORR) was 38.46% for the observation group, and 9.76% for the control group, which were statistically different (P<0.05). After treatment, the observation group presented remarkable improvement in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC and carbon monoxide diffusion function (DLCO), compared with those before treatment; these changes were also superior to those in the control group (P<0.05). Furthermore, the observation group showed significant decreases in the levels of serum cytokeratin 19 fragment antibody (CYFRA21-1), squamous cell carcinoma antigen (SCCA) and carbohydrate antigen (CA125) (P<0.05) as well as increases in the levels of CD3⁺ and CD4⁺, compared with those before treatment. Conclusions Treatment with PD-1 inhibitor can result in remarkably improved pulmonary function and clinical effectiveness in NSCLC patients at stage Ⅲ and Ⅳ, with good safety.