The protein ARHGDIA has been found to play distinct roles in cancer progression for several tumors. However, it remains elusive whether and how ARHGDIA plays functions in human glioma. In this study, we discovered that ARHGDIA is much downregulated in human glioma; meanwhile, its expression negatively correlates with glioma malignancy and positively relates to prognosis of glioma patients. It has independent predictive value of ARHGDIA expression level for overall survival of human glioma patients. Glioma patients with ARHGDIA-positive expression have a longer overall survival time than ARHGDIA-negative patients. Knockdown of ARHGDIA promotes cell proliferation, cell cycle progression, and cell migration due to the activation of Rho GTPases (Rac1, Cdc42, and RhoA) and Akt phosphorylation, whereas overexpression of ARHGDIA suppresses cell growth, cell cycle progression, and cell migration. ARHGDIA is a potential prognostic marker and therapeutic target for human glioma.