Abstract: OBJECTIVE   To explore the synergistic effect and possible molecular mechanism of TCM active compound Galangin and targeting drug Gefitinib on lung cancer.METHODS   The growth inhibition and apoptosis-promoting effect of Gefitinib and Galangin on A549 cells were detected by CCK-8 and flow cytometry, respectively. Western blot was used to detect the protein expression levels of apoptosis-related proteins and signal proteins in each groups.RESULTS   The combination for appropriate concentration of Galangin and Gefitinib more effectively inhibited the proliferation and promoted apoptosis of A549 cells, showing a good synergistic effect. The combination index (CI) measured by CompuSyn software less than 1. The results of Western blot showed that compared with Gefitinib alone, the combination of the two drugs further reduced the protein levels of p-EGFR, p-STAT3 and Bcl-2, and increased the protein levels of Cleaved Caspase-3, Cleaved PARP and Bax.CONCLUSION   In vitro, the combination of Galangin and Gefitinib have synergistic effects in the treatment of non-small cell lung cancer, and the inhibition of the proteins expression related to EGFR/STAT3 signal pathway may be one of the mechanisms, suggesting that the synergistic anticancer mode of the combination for the two drugs should be concerned.