Osteosarcoma (OS) is the leading cause of cancer‑associated mortality in adolescents and children. MicroRNAs (miRNAs) have critical roles in cancer, particularly in the initiation and progression of OS. Therefore, OS‑associated miRNAs should be identified for use as therapeutic targets for treatment of OS. This study aimed to investigate the expression pattern, potential roles and underlying mechanism of microRNA‑625 (miR‑625) in OS. miR‑625 was markedly downregulated in OS tissues and cell lines compared with that in associated adjacent non‑tumor tissues and human normal osteoblasts, respectively. The enforced expression of miR‑625 using miRNA mimics significantly reduced the proliferation and invasion of OS cells. Bioinformatics analysis and luciferase reporter assays indicated that miR‑625 targeted the 3'‑untranslated region of Yes‑associated protein 1 (YAP‑1). Furthermore, upregulation of miR‑625 reduced endogenous YAP1 expression at the mRNA and protein levels. The upregulated expression of YAP1 in OS tissues was inversely correlated with miR‑625 expression. YAP1 restoration using a recombinant plasmid rescued the miR‑625‑mediated tumor‑suppressive effects in OS cells. In conclusion, miR‑625 attenuated the cell proliferation and invasion of OS by suppressing YAP1. Thus, miR‑625 may be a potential target for OS therapy.