Background: The survival of patients with osteosarcoma has reached a plateau. Resistance to chemotherapy is a major obstacle to the effective treatment of osteosarcoma. Accordingly, search for novel agents focused on different mechanisms is needed. We have previously observed that sorafenib, a multikinase inhibitor, inhibit the i＞기울림꼴/i＞in vitroi＞기울림꼴/i＞ proliferation and enhance the radiosensitivity of osteosarcoma cells. We aimed to investigate the in vitro efficacy of sorafenib using mouse xenograft model. And to simulate the clinical setting, we established a chemo-resistant osteosarcoma cell lines and analyzed whether the growth of these cells are also influenced by sorafenib. Methods: Mouse xenograft model was established by injecting 3×10sup＞6/sup＞ KHOS/NP cells subcutaneously into BALB/c nude mice. When tumor size reached 180−200 mm3, the mice were treated daily with 30 mg/kg of sorafenib (BAY 43-9006, LC Laboratories, USA) by intraperitoneal injection for 7 days. Tumor growth was monitored biweekly by measuring the volume using formula (a×b×c)/2, where a, and b are the short and long diameter of tumor and c is the thickness, respectively. Cisplatin-resistant (CR) variants of each cell line were derived from each original parental ( PT) osteosarcoma cell line by continuous exposure to cisplatin (Sigma-Aldrich, UK). The sensitivity to sorafenib of the CR-osteosarcoma cells were measured by MTT (3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Results: In mouse xenograft model studies, sorafenib delayed the tumor growth. The tumor doubling time of the mice treated with sorafenib (n=7) was median 6.0 days (range, 3−7 days) and that of the control group (n=7) was 3.79 days (range, 2−5 days) (i＞기울림꼴/i＞Pi＞기울림꼴/i＞=0.03). Using HOS, KHOS/NP, MG63, U2OS cell lines, we established cisplatin-resistant osteosarcoma cell lines (OS-CR), each with IC50 values 3-4 times of the original parental cell lines. And we observed that sorafenib (3 μM) also inhibits the proliferation of these OS-CR cells. Conclusion: Still further studies are necessary, we hope a therapeutic potential of sorafenib and possibilities of using it as a potential adjuvant therapy for osteosarcoma.