Abstract: Objective：To investigate the expression of Ezrin in osteosarcoma pre-and post- chemotherapy and the relationship between the positive rate of Ezrin and clinical pathological features. Methods ：The expressions of Ezrin protein were detected with immunohistochemical stain in 51 cases of osteosarcoma pre- and post -chemotherapy, 11 cases of osteoidosteoma, 7 cases of osteoblastoma and 8 cases of newly formed bone in nonmalignant bone disease. Results ：No expression of Ezrin protein was found in 8 cases of newly formed bone.The expression rate of Ezrin was 9.09%,14.29%,56.86% in osteoidosteoma, osteoblastoma and osteosarcoma groups respectively.The positive rate of Ezrin protein in osteosarcoma group was significantly higher than that in osteoidosteoma, osteoblastoma and newly formed bone in nonmalignant bone diseases group (P<0.005).The expression of Ezrin protein in osteosarcoma group became low or disappear after chemotherapy（P=0.015）.But the expression of Ezrin had no relationship with tumor cell necrosis rate （TCNR）.The positive rate of Ezrin protein in post-chemotherapy osteosarcoma group with pulmonary metastasis was higher than that in cases without（P=0.029）.The positive expression rate of Ezrin protein in osteosarcoma cases when patients died in two years was higher than in cases when patients lived for more than two years （P=0.028）. Conclusion ：The positive rate of Ezrin in osteosarcoma was significantly higher than that in nonmalignant bone tumors.The detection of Ezrin protein may be a helpful marker in identification of benign and malignant bone tumors.Ezrin protein has close relationship with metastasis and prognosis in osteosarcoma.The expression of Ezrin protein in osteosarcoma group decreased after chemotherapy, which may evaluate the effect of preoperative chemotherapy to some degree.