Objective: To investigate the role of miRNA-200a in the efficacy of targeted therapy in non-small-cell lung cancer (NSCLC) patients and its underlying mechanisms. Methods: Real-time polymerase chain reaction and Western blot were used to investigate the level of miRNA-200a and FOXC1. The MTT assay，wound-healing and Transwell assays were performed to measure the effect of miRNA-200a and FOXC1 on cell growth, migration, invasion and other biological behaviors. Luciferase reporter assay analyzed the relationship between FOXC1 and miRNA-200a. Results: We found that a high level of miRNA-200a inhibited NSCLC cells growth, EMT, migration and invasion and increased sensitivity to gefitinib by targeting FOXC1. Furthermore, suppression of FOXC1 also inhibits cells progression and restores gefitinib resistance. Conclusion: Upregulated miRNA-200a or knockdown of FOXC1 enhanced sensitivity to gefitinib in NSCLCs. This may provide a novel effective therapeutic approach to overcome the acquisition of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy.