Abstract: Currently, histological and molecular methods are considered for the treatment of advanced non-small cell lung cancer (NSCLC). Single-agent epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase inhibitors (ALK-TKIs) have been used as standard first-line therapies for patients with active EGFR mutation and ALK rearrangement, respectively. However, to date, the single-agent EGFR-TKIs as the first-line therapy for patients with known EGFR mutations has been demonstrated to provide a prolonged progression-free survival but does not affect overall survival (OS). Physicians these days focus on improving the OS of patients with advanced NSCLC. To patients with EGFR mutation, combining and maintaining EGFR-TKIs with chemotherapy could be a promising approach. In this article, various ways of combining EGFR-TKIs with chemotherapy were explored.