Abstract: Objective To investigate the expressions of CD133 and CD44 in osteosarcoma tissue and their relationship with the prognosis of osteosarcoma. Methods Expressions of CD133 and CD44 were examined by immuno-histochemical MaxVision method in 79 specimens of human osteosarcoma tissues.The relationship between expression of CD133/CD44 and clinicopathological parameters was calculated by Chi-square test.Kaplan-Meier method was used to calculate the overall survival rate.The factors of gender,age,tumor-size,tumor location,Ennecking stage,local recurrence and lung metastasis were included in univariate analysis.The univariate analysis was used to determine the prognostic factors related with survival rate by Log rank test.The COX proportional-hazard regression model was used to analyze the correlation between the prognostic factor and survival. Results No correlations were found between expression of CD133/CD44 and clinicopathological parameters including gender,age,tumor location,tumor size,Ennecking stage and local recurrence,but occurrence of pulmonary metastasis was significantly associated with the expression levels of CD133/CD44(P value was 0.00014 and 0.0008,respectively).Univariate survival analysis showed that the significant prognostic factors were tumor size,local recurrence,lung metastasis,expression levels of CD133 and CD44.Multivariate analysis showed that CD133 and CD44 expression and tumor size were independent prognostic factors of patients with osteosarcoma. Conclusion The positive expressions of CD133 and CD44 closely correlate with the lung metastasis of osteosarcoma,detection of CD133 and CD44 may be used as an indicator for lung metastasis and prognosis of osteosarcoma.