Abstract: To investigate that possibility of multidrug resistance in lung cancer during Epithelialmesenchymal transition(EMT) through the Nrf2 signaling pahthway. Methods TGF-β1(10ng/ml) was used to induce EMT. The expression of EMT marker genes and nuclear Nrf2 were detected by Western blot. The level of GSH and the activity of GST were measured by colorimetry. MTT assay was used to measure the change of multidrug resistance during EMT. Results TGF-β1(10ng/ml) successfully induced lung adenocarcinoma cells A549 to mesenchymal transition: loss of cell polarity, the decreased expression of epithelial marker E-cadherin, but the increased expression of interstitial marker genes Snail and Vimentin. After the treatment of TGF-β1, the nuclear Nrf2 expression was significantly increased, simultaneously, the level of GSH and the activity of GST were profoundly increased. MTT displayed that the relative multidrug resistance to cisplatin in lung cancer cells was increased by 7.7 times. Conclusion During EMT, lung cancer cells show multidrug resistance, partially through Nrf2 signaling pathway.