To explore the tumor targeted therapy for patients with ALK mutation positive lung squamous cell carcinoma and to improve the level of diagnosis and treatment. This paper reports a case of ALK mutation positive lung squamous cell carcinoma and its targeted therapy, and reviews the relevant literature at home and abroad. The patient, male, 54 years old, suffered from “dry cough with fever for more than 1 month” be hospitalized. Lung squamous cell carcinoma was diagnosed by tracheoscopic biopsy. Gene detection (NGS) showed EML4-ALK gene fusion. The patients were treated with targeted combination chemotherapy of afatinib for 2 cycles, followed by targeted treatment of single drug afatinib for 6 weeks, and the CT reexamination showed the progress of the disease. It is speculated that lung squamous cell carcinoma with ALK rearrangement may have a low response to afatinib. But ALK gene fusion in lung squamous cell carcinoma is very rare, the therapeutic effect of afatinib on patients with ALK gene mutation positive lung squamous cell carcinoma needs to be confirmed by further research.