Abstract: Objective To observe the influence of up-regulating miR-200c expression on the sensitivity of lung cancer cells A549 to paclitaxel, gefitinib and the combination of two drugs and related mechanism. Methods miR-200c was transfected into lung cancer cells A549 using Lipofectamine 2000. The expression of miR-200c was detected by Real-time PCR. Drug sensitivity and cell apoptosis were analyzed with MTT assay and flow cytometry. Western blot was used to detect the expression of TUBB3 protein, EGFR, Akt, MAPK expression of phosphorylated proteins and total proteins. Results The sensitivity of A549 cells to paclitaxel and gefitinib and cell apoptosis were increased after up-regulation of miR-200c expression, but there was no obvious effect to the combination of two drugs. Western blot showed that miR-200c combined with paclitaxel inhibited the expression of TUBB3 protein; miR-200c combined with gefitinib inhibited the expression of EGFR, Akt phosphorylation protein, but there was no obvious difference when miR-200c combined with the combination of two drugs. Conclusion miR-200c could increase the sensitivity of lung cancer cells A549 to paclitaxel and gefitinib, which maybe respectively related to the inhibition of TUBB3 and EGFR, Akt phosphorylation protein, while there is no synergistic antitumor effect on the combination of two drugs.