Development of targeted therapies for squamous cell lung cancer (SqCLC) is currently limited by the prevalence of activating mutations and their predicting power of treatment efficacy. In the present study, we describe a case of treatment-naïve stage IIIB SqCLC that harbored a rare epidermal growth factor receptor (EGFR) p.E746_S752delinsV mutation with clinical complete response to neoadjuvant gefitinib. Pathological complete response was confirmed after surgical resection. No disease recurrence was documented after 20-month follow-up. This report suggested that first-generation EGFR tyrosine kinase inhibitor (TKI) could be an option in neoadjuvant context for advanced SqCLC patients harboring EGFR p.E746_S752delinsV mutation and highlighted the clinical benefits of EGFR testing in SqCLC patients who are females and never/former light smokers.