Abstract: Objective To investigate the effect and mechanism of FOXA1 on 17β-E2 induced epithelial mesenchymal transition in Ishikawa cells. Methods Ishikawa and HEC-1A cells were treated with 17β-E2 with different concentrations (0, 10-10, 10-8 and 10 -6mol/L), Ishikawa and HEC-1A Cell EMT markers E-cad and Vimentin and related factors of protein and mRNA expression levels were determined by westenblot aasay. The expression of E-cadherin、Vimentin、 ERα in protein expression levels were measured by Western Blot in normal control group, EMT model group, plasmid empty vector group， siFOXA1group or FOXA1overexpession group.Transwell invasion assay test Cell invasiveness. Results With the increase of E2 concentration, the expression of E-cad protein in Ishikawa cells was significantly decreased (P <0.01) and Vimentin protein expression was significantly increased (P <0.01). After treated with different concentrations of E2, the expression of E-cad and Vimentin in HEC-1A cells had no significant change (P> 0.05).To determine the role of FOXA1 in the 17β-E2 induced EMT of EC cells, Ishikawa cells were transiently transfected with siRNA against FOXA1 and we found that FOXA1 silence increased the invasive potential of Ishikawa cells(P <0.01).In comparison with the effect of FOXA1 knockdown,overexpressing of FOXA1 in Ishikawa cells had an opposite effect.When FOXA1 was overexpressed, it was not able to induce the occurrence of EMT by treating the Ishikawa cells with 17β-E2.We also found that the expression of ERα, which are downstream target of FOXA1, was promoted by FOXA1 up-regulation or inhibited by FOXA1 down-regulation. Conclusions FOXA1 inhibits 17β-E2-induced EMT in Ishikawa cells by upregulating ERα expression,while depletion expression of FOXA1 in Ishikawa cells promoted 17β-E2 induced EMT via inhibiting the expression of ERα