〔Abstract〕 Objective To investigate the expression of CD155/TIGIT in patients with osteosarcoma and its significance. Methods The expression differences of CD155 and TIGIT in tumor tissues of distant metastatic osteosarcoma patients and non-metastatic osteosarcoma patients were analyzed by cancer Genome Atlas(TCGA) database. The surgically removed tissues of osteosarcoma patients were collected to prepare pathological sections and tissue chips, and the tumor tissue and cell morphology were observed by HE staining. Immunohistochemical staining was used to detect the expression of CD155 and TIGIT, and the scores were divided into high expression group and low expression group according to the scores. Chi-square test was used to analyze the relationship between CD155/TIGIT expression and clinical features and prognosis. Results TCGA database data showed higher expression of CD155 and TIGIT in patients with osteosarcoma accompanied by metastasis. HE staining of pathological sections revealed that tumor tissues with high expression of CD155/TIGIT contained more binuclear or multinucleated, hyperchromatic and obviously heteromorphic tumor cells. Immunohistochemical staining and score analysis of tissue chip showed that the expression of CD155 and TIGIT was correlated with clinical stage and distant metastasis(P<0.05), but not with age, sex, tumor size, pathological type and tumor necrosis rate. Conclusion CD155 and TIGIT may be one of the prognostic indicators of osteosarcoma.