Objective To study the effect of Tirelizumab combined with NP (N: vinorelbine; P: cisplatin/carboplatin) chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC). Methods A total of 86 patients with NSCLC admitted to our hospital from March 2022 to December 2023 were selected and divided into NP group (42 cases) and combined group (44 cases) according to different treatment schemes. The NP group was treated with NP chemotherapy, and the combined group was treated with Tirelizumab combined with NP chemotherapy. The clinical efficacy, tumor markers [squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), soluble cytokeratin 19 (CYFRA21-1)], serum levels of marker protein [gene Kirsten-Rous arcomaviral oncogene homolog (K-ras), Golgi protein-73 (GP-73), nucleotide excision repair cross complementation group 1 (ERCC1)], T cell subsets levels (CD3+^{, CD4}+^{, CD8}+^{, CD4}+^/CD8+), and the incidence of toxic and side effects were compared between the two groups. Results The total effective rate of the combined group (88.64%) was higher than that of the NP group (69.05%) (P<0.05), and there was no significant difference in the incidence of toxic and side effects between the two groups (P>0.05); compared with before treatment, the levels of SCC, CA125, CEA, CYFRA21-1,GP-73, ERCC1, K-ras, CD3+^{, CD4}+^{, CD4}+^/CD8+^{, CD8+} in the two groups were decreased, the improvement of the combined group was more significant (P<0.05). Conclusion The effect of Tirelizumab combined with NP chemotherapy in the treatment of NSCLC patients is significant, which can effectively control disease progression, enhance immune function, reduce serum protein levels, and inhibit tumor growth.