Gefitinib and Erlotinib both are the first-generation oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which have excellent antitumor effects against advanced or recurrent non-small cell lung cancer (NSCLC). Despite initially showing a good response, most patients present with recurrence of the disease; this is due to the development of resistance to EGFR-TKIs. Since the lack of a standard therapeutic option for NSCLC patients who have progressive disease after EGFRTKIs failure, this article discussed the subsequent treatment choices for patients with acquired resistance to gefitinib by an EGFR mutation with advanced adenocarcinoma male patient.