MicroRNAs (miRNAs) are non-coding small RNAs that have been shown to play a key role in the development of many tumors. However, its specific mechanism of action in non-small cell lung cancer (NSCLC) is not very clear. This study was to identify the effect of miRNA-449a on NSCLC invasion and migration. We used quantitative real-time PCR experiments to demonstrate that miRNA-449a is down-regulated in NSCLC tissues and cell lines. We also used the Transwell assay to detect cell invasion and migration, and the Western Blot assay  was used to detect protein expression. The dual luciferase assay was used to detect the targeting relationship between miR-449a and A Disintegrin And Metalloproteinases 10 (ADAM10). Our experiments demonstrated that miRNA-449a was down-regulated in NSCLC tissues and cell lines. When miRNA-449a was up-regulated in NSCLC cells, the invasion and migration ability of the cells was weakened, and the expression of ADAM10 was decreased. After down-regulation of miRNA-449a, the cell's invasion and migration ability was enhanced, and the expression of ADAM10 was increased. Through dual luciferase assays, we also found that miRNA-449a can target ADAM10 to delay the progression of epithelial-mesenchymal transition (EMT) and inhibit invasion and migration. Our experiments demonstrated that miRNA-449a acted as a tumor suppressor gene through inhibiting the expression of ADAM10 in NSCLC.