MicroRNAs (miRNAs) are a class of short, noncoding RNAs that act a crucial role in tumor development. Previous studies showed that miR-448 expression was deregulated in many tumors. However, the role of miR-448 in gastric cancer (GC) remains unknown. In our study, we demonstrated that miR-448 expression was downregulated in GC tissues compared with the corresponding nontumor tissues. We also showed that miR-448 expression was downregulated in GC cell lines. Ectopic expression of miR-448 suppressed GC cell proliferation, colony formation, and invasion. Moreover, we identified A Disintegrin And Metalloproteinases 10 (ADAM10) as a direct target gene of miR-448 in GC cell. ADAM10 expression was upregulated in GC tissues and cells. Furthermore, the expression level of miR-448 was negatively correlated with the expression level of ADAM10 in GC tissues. Moreover, ADAM10 overexpression rescued the effect of miR-448-mediated GC cell proliferation, colony formation, and invasion. These results demonstrated that miR-448 might play as a tumor suppressor miRNA partly through targeting ADAM10 expression.