Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 inhuman osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then theprecise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expressionvector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantlysuppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwellswere dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasionand metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This wasconfirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomasby down-regulating TIAM1, MMP2 and MMP9 expression.