Abstract: OBJECTIVE To investigate the ethanol extract of Hedyotis diffusa(EEHD) and gefitinib(Gef) used on the human lung adenocarcinoma H358 cell, which has been induced to epithelial mesenchymal transition by transforming growth factor beta 1(TGF-β₁) in vitro. METHODS The H358 cells were successfully induced to the epithelial mesenchymal transformation model by 5 ng·mL^-1 TGF-β₁ for 24 h. After preparation of the EEHD, respectively added EEHD for 48 h(Group A), Gef for 48 h(Group B), EEHD for 24 h and then Gef for 24 h(Group A24B24), Gef for 24 h and then EEHD for 24 h(Group B24A24), EEHD combined with Gef for 48 h(Group AB) and the control group to the model cells. Then the rates of cell growth were detected by CCK-8 test, the protein expression of epithelial marker (E-cadherin) and mesenchymal cell marker (Vimentin) were detected by Western-blot. And the rates of apoptosis were tested by flow cytometry. RESULTS In all other groups, the expression of E-cadherin increased while the expression of Vimentin decreased than the control group. The rates of cell growth inhibition and apoptosis of EEHD combined with gefitinib group were significantly higher than gefitinib monotherapy group’s, and the expressions of EGFR, Vimentin were significantly lower than gefitinib monotherapy group’s, while the expressions of E-cadherin was higher than gefitinib monotherapy group’s, P<0.05. There was no statistically significant difference between the groups of different orders(A24B24 and B24A24). CONCLUSION Hedyotis diffusa and gefitinib have a combined effect for the epithelial mesenchymal transition(EMT) and tumor cell growth process. Hedyotis diffusa have partially reversal effect on H358 which has been induced by TGF-β1 to epithelial mesenchymal transformation model. Hedyotis diffusa can partially reverse the EGFR-TKI resistance problems caused by EMT.