Osteosarcoma is the most common type of malignant bone tumor, often affecting adolescents and children. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in osteosarcoma tumorigenesis. In our study, we demonstrated that miR-448 expression was downregulated in osteosarcoma tissues and cell lines. Overexpression of miR-448 suppressed osteosarcoma cell proliferation, colony formation and migration. Moreover, we found that EPHA7 was a direct target gene of miR-448 in osteosarcoma cells. We further demonstrated that the EPHA7 expression level was upregulated in osteosarcoma tissues. Interestingly, the expression level of EPHA7 was inversely correlated with the expression level of miR-448 in osteosarcoma tissues. In addition, elevated expression of miR-448 suppressed osteosarcoma cell proliferation and invasion through targeting EPHA7. Taken together, these findings suggest that miR-448 functioned as a tumor suppressor gene in the development of osteosarcoma through targeting EPHA7.