Purpose: The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors. We determined c-Met expression and signaling in human osteosarcoma cells and tested the ability of c-Met tyrosine kinase inhibitors (TKI) to block HGF-induced biological signaling. Methods: Expression and signaling were determined using western blot. Biological end points included wound healing, cell proliferation, and invasion. SU 111274, one of C-Met TKI was tested for their ability to block HGF-induced signaling. Results: c-Met was expressed and functional in osteosarcoma cells. Activation of c-Met promoted phosphorylation of AKT and MAPK. Cell growth and wound healing were also stimulated by HGF. SU11274 blocked HGF-induced signaling and wound healing. Conclusions: These results support the hypothesis that involvement c-Met and HGF-SF in the growth and progression of human osteosarcoma. Blocking the HGF/c-Met pathway may be clinically useful for the treatment of osteosarcoma.