Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the standard treatment for -mutated non-small cell lung cancer (NSCLC), although a small subset of patients does not respond to EGFR-TKI, especially in patients with a smoking history and squamous cell histology. Additionally, even given an initial good response, acquired resistance to EGFR-TKI is inevitable. More individualized treatment could be necessary in certain types of -mutated NSCLC. We herein report a case of -mutated metastatic lung squamous cell carcinoma with a high tumor proportion score (TPS) of programmed death ligand 1 (PD-L1), where chemotherapy plus pembrolizumab therapy had a durable efficacy. In this case, chemotherapy plus pembrolizumab therapy was administered, though EGFR-TKI is the standard first-line therapy of -mutated NSCLC. Three years after treatment initiation, no sign of recurrence was observed. This case suggests that a detailed evaluation of a patient's background is important in making an effective personalized therapeutic strategy.