This study aims to detect the expression of heat shock protein gp96(HSPgp96)in osteosarcoma and explore its role in anti-tumor immunity.Expression of HSPgp96 in 45 cases of osteosarcoma,including 24 cases of the osteoblast type,21 cases of chondroblast type and 5 cases of normal bone tissue were detected by immunohistochemistry(IHC).The expression rate of HSPgp96 was 100%(45/45)in osteosarcoma,compared with 20% (1/5)in normal bone tissue.The average positive cell rates were 97.23% and 0.48% in osteosarcoma and normal bone tissue,respectively,and the difference between them was significant(P＜0.01).The positive cell rates in osteoblast type and chondroblast type were 97.78% and 96.56%,respectively,and the difference had no statistical significance(P＞0.05).The expression degree of HSPgp96 in osteosarcoma had a clear correlation with the pathologic degree(P＜0.05),while it had no relationship with the clinical stage(P＞0.05).The expression of HSPgp96 is high in osteosarcoma and it may be a significant index for judgment of malignancy degree and an important target site of anti-tumor immunity.