Dysregulation of microRNA (miRNA) expression is a critical event in the development and progression of non-small-cell lung cancer (NSCLC). miR-384 has been identified as a novel cancer-related miRNA in numerous cancers, but little is known about its role and functional mechanism in NSCLC. In this study, we found that miR-384 was significantly downregulated in NSCLC tissues and cell lines. The overexpression of miR-384 repressed the growth and invasion of NSCLC cells, whereas its suppression showed the opposite effect. Moreover, astrocyte elevated gene-1 (AEG-1) was identified as a target gene of miR-384. The overexpression of miR-384 significantly decreased AEG-1 expression and Wnt signaling, whereas its suppression promoted this pathway. Furthermore, miR-384 was inversely correlated with AEG-1 expression in NSCLC tissues. Additionally, restoration of AEG-1 expression in miR-384-overexpressing cells significantly reversed the antitumor effects of miR-384. Taken together, these results reveal that miR-384 represses the growth and invasion of NSCLC cells by targeting AEG-1. Our study suggest that miR-384 and AEG-1 may serve as potential targets for the diagnosis and treatment of NSCLC.