Aims:　Osteosarcoma　is　the　most　frequent　primary　malignant　bone　tumor　in　children　and　adolescents.　Identifying　specific　and　sensitive　biomarkers　is　beneficial　to　early　detection　and　improvement　of　life　qualities　and　overall　survival　rates　of　osteosarcoma　patients.　Materials　and　methods:　Realtime　PCR　was　used　to　detect　the　expression　of　miR-598.　CCK-8　assay　was　employed　to　detect　the　proliferation　of　osteosarcoma　cells,　while　transwell　assays　were　used　to　examine　the　migration　and　invasion.　Tumor　xenograft　experiments　were　performed　to　test　the　in　vivo　malignancy　of　osteosarcoma　cells.　Co-culture　experiment　was　used　to　study　the　relationship　between　osteosarcoma　cells　and　osteoblast.　Realtime　PCR,　Western　Blotting　and　luciferase　report　assays　were　conducted　for　the　target　genes　analysis.　Key　findings:　Using　a　cohort　of　20　cases　of　osteosarcoma　and　paired　adjacent　tissue　samples,　we　found　that　miR-598　expression　was　decreased　in　osteosarcoma　tissues　and　serum,　as　well　as　the　osteosarcoma　cell　lines.　Over　expression　of　miR-598　suppressed　the　proliferation,　migration,　and　invasion　of　osteosarcoma　cells,　while　inhibition　of　miR-598　expression　stimulated　the　proliferation,　migration,　and　invasion.　However,　MiR-598　had　no　effect　on　osteosarcoma　cell　apoptosis.　Data　from　nude　mice　further　demonstrated　the　inhibitory　role　of　miR-598　in　osteosarcoma　progression　in　vivo.　Mechanically,　miR-598　played　its　role　by　modulating　osteoblastic　differentiation　in　the　microenvironment　and　targeting　PDGFB　and　MET.　Significance:　Our　findings　enrich　the　knowledge　of　miR-598　in　osteosarcoma　progression,　and　reveal　miR-598　as　a　promising　diagnostic,　prognostic,　therapeutic　biomarker　for　osteosarcoma.