Objective To study human lung adenocarcinoma cell line A-549 treated with antagonist and agonist of potassium channel how to affect metastasis of A-549 and its mechanism. Methods Invasion and migration capability of A-549 in vitro was evaluated by using transwell chamber model. Alteration of cytoskeleton was observed through immunofluorescence. Western blotting were used to detect the protein expression of Ezrin and HuR in A-549 cell lines while Glibenclamde and Pinacidil were applied to them. Results In the presence of the antagonist Glibenclamide, migration of A-549 was inhibited by (57.18±5.46)% and invasion was inhibited by (54.92±3.72)% in the transwell assay, meanwhile A-549 manifested disorder of microtubule and more orderly microfilament. And agonist of the potassium channel had an contrary effect on A-549. Ezrin and HuR protein were successfully down-regulated in A-549 treated with Glibenclamide and upregulated in A-549 treated with pinacidil. Conclusion Functional alterations of the potassium channel affects capability of migration and invision of A-549, which is associated with different expression of ezrin and HuR protein that modify cytoskeleton.