Abstract: Objective:To explore the correlation of the drug susceptibility of gefitinib-resistant in non-small cell lung cancer(NSCLS) induced by T790M mutation in EGFR and signal transducers and activators of transcription 3(STAT3).Methods:H1975 and PC9 cells were dealed with different concentrations of STAT3 specific inhibitor JSI-124.The inhibition rate of cells and the levels of protein and mRNA of relative factors were determined by CCK-8,Western blot and RT-PCR,respectirely.Results:The STAT3 expression of H1975 cells with EGFR T790M mutation of NSCLC were obviously higher than that in PC9 cells(P0.01).JSI-124 inhibited the activity of STAT3 in H1975 mutation cells in dose-and time-dependent manner and improved the susceptibility of gefitinib,but not for PC9 cells.Conclusions:The gefitinib-resistant mechanism induced by T790M mutation in EGFR is related to STAT3,which can be reversed by inhibiting the STAT3 activity.