The NUP58 gene encodes a nucleus-pore protein that is a component of nuclear pore complex (NPC). NPC facilitates the transportation of macromolecules (ions and other substances) into the nuclei of eukaryotic cells. However, there are no relevant reports about the NUP58 gene in human lung cancer. In this study, we demonstrated that NUP58 was highly expressed in the primary and metastatic foci of lung adenocarcinoma, with low expression in adjacent tissues and normal lung tissue. In patients with lung adenocarcinoma, the NUP58 gene was highly expressed in patients with stage IV disease (P < 0.05); NUP58 knockdown using a lentiviral vector-mediated shRNA inhibited metastasis and invasion of lung adenocarcinoma cell lines A549 and H1299 in vivo and in vitro. Furthermore, silencing of NUP58 resulted in altered expression of EMT markers, associated GSK-3β/Snail pathways, tumor metastasis and invasion factors. In conclusion, these findings demonstrated that NUP58 can promote the metastasis and invasion of lung adenocarcinoma, which can be partially attributed to the GSK-3β/Snail signaling pathway.