To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK-positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China. This retrospective study analyzed data for 36 advanced-stage patients with ALK-positive LUSC (cohort A) and 13 patients with ALK-positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once-daily ensartinib 225mg. Outcome analysis included the demographic characteristics, tumor response, progression-free survival (PFS), and treatment-related adverse events (TRAE). Among the 49 patients, the majority were under 65 years old (73.5%), non-smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0-1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE. Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes.