Abstract: Objective To investigate the expression and clinical significance of Wnt5a and receptor tyrosine kinase-like orphan receptor 1（ROR1） proteins in human osteosarcomatous tissues. Methods The expression of Wnt5a and ROR1 in 35 specimens of osteosarcoma tissues and 15 specimens of osteochondroma tissues was detected by immunohistochemical SP method. The correlation of Wnt5a and ROR1 expression with clinicopathological characteristics and prognosis of the patients with osteosarcoma was analyzed. Results The positive expression rates of Wnt5a and ROR1 in osteosarcoma tissues were 62.9％（22／35）and 57.1％（20／35），significantly higher than 13.3％（2／15）and 6.7％（1／15） of osteochondroma tissues, and the difference was statistically significant（P＜0.05）. The expression of Wnt5a and ROR1 was positively related to Enneking clinica1 stages and metastasis （P＜0.05）. The expression of Wnt5a was positively correlated with ROR1 protein （r=0.888， P＜0.001）. Kaplan-Meier analysis showed that the median overall survival of osteosarcoma patients with positive Wnt5a and ROR1 expression were 23 months and 27 months， significantly shorter than 41 months and 42 months of negative expression patients（P＜005）. Conclusion Wnt5a and ROR1 were high.y expressed in osteosarcoma and associated with the development and progression of osteosarcoma. Combined detection of Wnt5a and ROR1 is of great significance in judging the progress and prognosis of osteosarcoma.