Recent profiling and functional studies have demonstrated that a panel of miRNAs (miR-608, − 4513, − 497, −499a [3], −23a [4] and et al.)are aberrantly expressed in EGFR-TKIs-resistant NSCLC, and dysregulation of these miRNAs regulates fundamentally the pathogenesis of EGFR-TKIs resistance via modulation of multiple cancerous functions including deregulated cell proliferation/apoptosis, maintenance of cancer stem cells and activation of alternative signaling (HGF, Met, AXL and IGF-1R). The gene discussed is EGFR; the disease is non-small cell lung carcinoma.