Objective：To evaluate the efficacy and safety of tislelizumab combined with chemotherapy as first -line treatment for locally advanced or metastatic squamous non - small - cell lung cancer in the real -world. Methods：A total of 109 patients with lung squamous cell carcinoma were included in the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2023，of whom 66 patients in the tislelizumab combined with chemotherapy group and 43 patients in the chemotherapy group. The objective response rate（ORR），progression-free survival（PFS），overall survival（OS）and the incidence of treatment-related adverse events（TRAEs）of the two groups were evaluated. Results：At a median follow-up of 20.2 months，the ORR of the tislelizumab combined with chemotherapy group was significantly higher than that of the chemotherapy group（75.8% vs. 51.2%）. The median PFS prolonged significantly in the tislelizumab combined with chemotherapy group compared to the chemotherapy group（17.3 months vs. 9.3 months）. OS data were not reached in the tislelizumab combined with chemotherapy group，which was significantly longer than the chemotherapy group（19.3 months，HR=0.38，95%CI：0.19-0.68，P=0.002）. The incidence of overall TRAEs and TRAEs above grade 3 in the two groups was similar. The incidence of immune-related adverse events（irAEs）in the tislelizumab combined chemotherapy group was 28.8%，including one case（1.5%）of grade 3 and above immune-associated pneumonia. Conclusion：Tislelizumab combined with chemotherapy as first-line treatment significantly improves the efficacy and manageable safety/tolerability profile in patients with locally advanced or metastatic lung squamous cell carcinoma.