MicroRNAs have emerged as promising molecular factors with potential for clinical applications in cancer diagnosis and therapy. In the present study, we demonstrated that the level of miR-200c in lung cancer tissues was lower than that in normal tissues using real-time PCR. To further investigate the effects of miR-200c expression in lung cancer cells, we upregulated miR-200c levels in H460 cells using transfection. We found that the percentage of apoptotic cells was higher in the cells expressing miR-200c than that in the untransfected cells. Furthermore, the antitumor activities of miR-200c were demonstrated in vivo. Notably, we confirmed that reservatol (RESV) showed stronger antitumor activities in miR-200c-positive cells than in miR-200c-negative cells. Finally, we demonstrated that expression of miR-200c in H460 cells suppressed cell growth by targeting RECK, followed by activation of the JNK signaling pathway and ER stress. Collectively, these data show that miR-200c expression sensitizes H460 cells to RESV and this is likely due to RECK expression.