Glioma is one of the most common solid tumors, and the molecular mechanism for this disease is poorly understood. EphB4 tyrosine kinase receptor has been involved in various physiologic and pathologic processes, and the role of EphB4 in tumorigenesis has recently attracted much interest. However, its function in glioma remains largely unknown. In this study, we explored the function of EphB4 in glioma. We found that the expression of EphB4 was significantly upregulated in clinical glioma samples. Overexpression of EphB4 in glioma cell lines accelerated cell growth and tumorigenesis. In contrast, downregulation of EphB4 inhibited cell growth. Furthermore, we showed that EphB4 promoted cell growth by promoting EGFR signaling. Taken together, our findings suggest that EphB4 plays an important role in the progression of glioma by stimulating cell growth and EphB4 might be a potential therapeutic target for glioma.