Abstract：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 efficacy and safety of the two groups were evaluated. Results: The objective response rate (ORR) in the Tislelizumab combined with chemotherapy group was significantly higher than that in the chemotherapy group (75.8% vs 51.2%). At a median follow-up of 20.2 months, the median progression-free survival (mPFS) has significantly prolonged in the Tislelizumab combined with chemotherapy group compared to chemotherapy group (17.3 months vs 9.3 months). Overall survival (OS) data were not reached in the Tislelizumab combined with chemotherapy group, which was significantly longer than the chemotherapy group (19.3 months). The incidence of overall adverse effects and adverse effects above grade 3 in the two groups was similar. The incidence of grade 3 and above adverse events in the Tislelizumab combined chemotherapy group was 28.8%, including 1 case (1.5%) of grade 3 immune-associated pneumonia. Conclusion: Compared with chemotherapy alone, 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.