Glioma is the most common human primary brain cancer with high mortality and unfavorable clinical outcome. Coagulation factor 2 thrombin receptor (F2R), is a key component in the thrombosis process and has been demonstrated upregulated in various cancers. However, the effect and molecular mechanisms of F2R in glioma remains unclear. In our study, we confirmed that the expression of F2R was upregulated in glioma and predicted poor prognosis. Gene Set Enrichment Analysis (GSEA) and function assays demonstrated that F2R overexpression promoted glioma cell proliferation, metastasis and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Then, we identified and validated F2R was the target gene of SRY-box 2 (SOX2) by dual luciferase reporter assay and chromatin immunoprecipitation assay. Besides, High expression of F2R in malignant glioma was associated with β-catenint signaling pathway activation. Our findings conclude that F2R promotes glioma cell proliferation and metastasis under SOX2 and actives WNT/β-catenin Signaling pathway, which provides novel insight to the therapeutic regimen in glioma.