Abstract: Objective：To investigate the role of microRNAs in Fox M1induced nonsmall cell lung cancer (NSCLC) epithelialmesenchymal transition (EMT). Methods：Over expression Fox M1 plasmid, Fox M1shRNA, miR539, miR4855p mimics and inhibitor were transfected into NSCLC cells. The expression of Fox M1 protein and mRNA, miR539 and miR4855p were detected by Western blotting and realtime PCR. The CCK8 and cell migration was used to observe the effect of Fox M1, miR539 and miR4855p on the proliferation and invasion of NSCLC. Luciferase reporter assay was used to explore the relationship between miRNA( miR539 and miR4855p) and EMT regulatory protein (ZEB1 and Snail1). Results：Realtime RTPCR and Western blotting showed Fox M1 over expression inhibited the expression of miR539, miR4855p, miR539 and miR4855p in NSCLC cells were increased after transfected Fox M1shRNA. MiR539 and miR4855p suppressed enhancement of proliferation and invasion of NSCLC cells by Fox M1. miR539 targeted and inhibited the translation of ZEB1,miR4855p targeted and inhibited the translation of Snail1 in NSCLC cells. Conclusions：The mechanism of Fox M1 upregulation of EMT protein is to decrease the expression of miR539 and miR4855p in NSCLC cells, thus to affect the proliferation and invasion of NSCLC cells, and to inhibit distant metastasis.