Objective To evaluate the expression of Integrin α2β1 in serum of osteosarcoma patients and to investigate the effect of Integrin α2β1 on metastasis of osteosarcoma. Methods Sandwich enzymelinked immunosorbent assay was applied to test Integrin α2β1 in serum of 26 healthy controls (male 16, female 10; age 18-32, average age 23.54±3.82) and 43 osteosarcoma patients (male 28, female 15;age 8-47,average age 18.42±9.10)before and after the surgery and the chemotherapy. The patients included osteoprogenitor cells type in 24 cases, fibroblast type in 9 cases, chondroblast type in 7 cases, and other types in 3cases; with Enneking stage ⅡA in 13 cases, stage ⅡB in 26 cases, stage Ⅲ in 4 cases. Among them, 22 patients receive the neo-adjuvant chemotherapy. After that, we compared the data of different groups. At the same time, in accordance with tumor size, position, clinical stage, histology grade and metastasis situation to categorize groups compared among the groups of serum Integrin α2β1 differences in order to explore its relationship with patients' prognosis and metastasis. Results The Integrin α2β1 of osteosarcoma patients in blood before the surgery was expressed highly. It was significantly higher than the control group. The expression before surgery had significant correlation with osteosarcoma Enneking clinical stages, tumor size and metastasis. And it was independent of tumor position and Dahlin histology grade. The expression of Integrin α2β1 in blood of the osteosarcoma patients after limb salvage surgery decreased significantly. And the expression of Integrin α2β1 in blood of patients receiving new adjuvant chemotherapy was significant differences before and after the chemotherapy. Conclusion The expression of Integrin α2β1 has positive correlation with the occurrence, development and metastasis of the osteosarcoma. It is probably a new biological indicator for diagnosis and estimating prognosis of osteosarcoma. Simultaneously surgery and new adjuvant chemotherapy are still effective methods to treat osteosarcoma.