Epithelial mesenchymal transition (EMT) has been shown to play a role in cellular differentiation during deve-lopment and tumor invasion. However, the precise molecular mechanisms of EMT are not fully elucidated. Previous studies suggested that the mechanism underlying the possible involvement of ezrin in EMT process might be different from that of moesin, another ERM protein. In our study, we examined the role of ezrin in actin filament reorganization and cell meta-stasis during TGF-β1-induced alveolar EMT. Suppressing ezrin expression limited morphological changes and actin filament remodeling, decreased cell migration and invasion during EMT. Immunofluorescence experiments indicated that EMT characteristics in lung cancer cells are associated to differential ezrin subcellular localization. We also found that podocalyxin interacted with ezrin after TGF-β1 induction. Therefore, ezrin is an important regulator of the EMT process, and its function might possibly be mediated by the ezrin-podocalyxin interaction during TGF-β1-induced alveolar EMT. Our finding provides important new insights into the mechanisms of action of the ERM proteins in the TGF-β1-induced alveolar EMT.