Glioma, one of the most common types of primary brain tumors, presents considerable challenges due to its poor prognosis. Emerging research has demonstrated a strong connection between Centromere Protein M(CENPM) and tumor progression. However, the precise role of CENPM in glioma remains poorly understood. This study delves into the involvement of CENPM in glioma progression. Data analysis revealed that heightened CENPM expression correlates with worse patient outcomes and is highly expressed in glioma. In vitro experiments showed that reducing CENPM expression inhibits glioma cell proliferation and induces G0/G1 phase cell cycle arrest. Furthermore, RNA-seq and Western Blot analyses demonstrated that CENPM activates the PI3K/AKT signaling pathway in glioma cells. In vivo experiments confirmed that knocking down CENPM leads to reduced tumor growth in glioma models and improves the prognosis of tumor-bearing mice. This study underscores the critical role of CENPM in glioma and sheds light on potential therapeutic strategies.