Abstract: Objective 　To investigate the expression of Skp2 and p27 and their association with clinical, histologic characteristics in osteosarcoma, the correlation between expression of Skp2 and p27 in osteosarcoma. Methods 　Skp2 protein and p27 protein were examined by using immunohistochemical SP staining method in 48 cases of osteosarcoma and 16 cases of osteochondroma. Results 　Negative expression of Skp2 was detected in all osteochondroma. In contrast, it was detected in 43. 75 %(21/ 48) of osteosarcoma. Positive expression of Skp2 was detected significantly more frequently in osteosarcoma than that of osteochondroma. Skp2 protein expression in osteosarcoma was positively associated with the clinical stage and differentiation. The positive rate of p27 protein in osteochondroma and osteosarcoma were 75 %(12/16) 、47. 92 % (23/ 48), significant difference was found between these two groups. p27 protein expression in osteosarcoma was negatively associated with the clinical stage and differentiation. Skp2 was inversely associated with expression of p27 in osteosarcoma. Conclusion 　Skp2 expression might play an important role in the development and progression of osteosarcoma via cyclin-depended kinase inhibitor p27 proteolysis, and the combined examination of Skp2 and p27 expression might be a guide for early diagnosis and a determinant of malignancy and prognosis of osteosarcoma.