The forkhead box A2 (FOXA2) is the key transcriptional factor that plays an important role in tumorigenesis. However, until now the expression pattern and role of FOXA2 in glioma have yet to be elucidated. Therefore, the aim of this study was to evaluate the expression of FOXA2 in glioma and investigate its role in glioma cells. Our data showed that FOXA2 was significantly downregulated in human glioma cell lines. Forced expression of FOXA2 suppressed the ability of glioma cells to proliferate, migrate, and invade and influenced the expression level of EMT-associated proteins. In addition, forced expression of FOXA2 attenuated tumor growth of glioma in a nude mouse xenograft model. Mechanistically, we disclosed that forced expression of FOXA2 greatly downregulated the expression of β-catenin, cyclin D1, and c-Myc in glioma cells. Taken together, these results show that FOXA2 may play an important role in proliferation, invasion, and tumorigenesis in glioma cells. Thus, FOXA2 may be a potential therapeutic target for the treatment of glioma.