Objective:To investigate the clinical efficacy and safety of programmed death protein 1 (PD-1) inhibitos combined with Fuzheng Kang'ai Decoction in patients with stage Ⅲ or Ⅳ non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis in real world.Methods:Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), total survival time (OS) and adverse events of patients with advanced or metastatic NSCLC who received PD-1 inhibitors for the first time in the Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine from August 2018 to March 2021 were retrospectively analyzed, and was prospectively followed up until September 2022. Kaplan-Meier method was used to plot survival curves and evaluate median PFS and median OS, while Cox proportional hazards regression model was used for multivariate analysis.Results:The final 66 patients were included in the study, with an ORR of 33.3% (22/66), a DCR of 86.4% (57/66), a median PFS of 9.90 months, and a median OS of 31.83 months. Univariate analysis showed that median PFS was associated with TNM stage, liver metastasis, PD-L1 expression level, lung immune prognostic index (LIPI), and traditional Chinese medicine syndrome types ( P values were 0.004, 0.033, 0.040, 0.004, and 0.001, respectively). Multivariate Cox regression analysis showed that TNM stage [ HR (95% CI)=4.179 (1.781, 9.804)], PD-L1 expression level 1%-49% [ HR (95% CI)=0.346 (0.127, 0.940)] or ≥ 50% [ HR (95% CI)=0.074 (0.019, 0.288)], LIPI [ HR (95% CI)=14.515 (2.939, 71.681)], and TCM characteristics of deficiency of yang qi [ HR (95% CI)=5.954 (2.093, 16.940)] were independent influencing factors for PFS. The overall and grade 3-5 treatment-related adverse events were 68.2% (45/66) and 9.1% (6/66), respectively. Conclusions:Fuzheng Kang'ai Decoction combined with PD-1 inhibitors is an effective and tolerable therapy for patients with advanced or metastatic NSCLC. TNM stage, liver metastasis, PD-L1 expression, LIPI and TCM characteristics are early predictors of clinical efficacy for patients with stage Ⅲ/Ⅳ NSCLC that receive traditional Chinese medicine combined with immunotherapy .