Objective To analyze the efficacy of immunotherapy combined with chemotherapy in the treatment of lung squamous cell carcinoma (LUSC) patients, to provide clinical reference. Methods The clinical data of 118 patients with LUSC admitted to Beijing Chaoyang Huanxing Cancer Hospital from January 2020 to January 2023 were retrospectively analyzed. According to different treatment plans, 118 LUSC patients were divided into the monotherapy immunotherapy group (13 cases), the monotherapy chemotherapy group (58 cases) and the immunotherapy combined chemotherapy group (47 cases). The clinical efficacy, levels of inflammatory cytokines [C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)], levels of tumor markers [squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA) and neuro-specific enolase (NSE)], lung function indicators [forced vital capacity (FVC), forced expiratory volume at 1 second (FEV 1 )and peak expiratory flow rate (PEF)], and incidence of adverse reactions among 3 groups of patients were compared. Results The total effective rate of patients in the immunotherapy combined chemotherapy group was higher than that in the monotherapy chemotherapy group and monotherapy immunotherapy group (all P <0.05). The levels of CRP, PCT and IL-6 at 7 days after treatment completion (T 1 ) in 3 groups were lower than 7 days before treatment (T 0 ), and the immune combined chemotherapy group were lower than that in the monotherapy chemotherapy group and monotherapy immunotherapy group (all P <0.05). The levels of SCC, CEA and NSE at T 1 in 3 groups were lower than T 0 , and the level of SCC, CEA in the immune combined chemotherapy group were lower than that in the monotherapy chemotherapy group and monotherapy immunotherapy group (all P <0.05). The levels of FVC, FEV 1 and PEF at T 1 in 3 groups were higher than T 0 , and the immune combined chemotherapy group were higher than the other two groups (all P <0.05). The incidence of myocarditis and decreased liver and kidney function of the monotherapy chemotherapy group were lower than the other two groups (all P <0.05). Conclusion Immunotherapy combined with chemotherapy is more effective than monotherapy and monotherapy in treating LUSC patients, and can improve inflammatory response and lung function, reduce the level of tumor markers.