FEZ family zinc finger 1 (FEZF1) is an essential transcription factor during olfactory development. In gastrointestinal tumors， FEZF1 plays an oncogenic role through DNA demethylation. However， the role of FEZF1 in the prognosis of human glioma prognosis remains unclear. In this research， we discovered that FEZF1 was significantly increased in glioma tissues in contrast to normal brain tissues (NBTs; P < 0.05). Moreover， the expression of FEZF1 showed a significant correlation with Eastern Cooperative Oncology Group performance status， World Health Organization grade， isocitrate dehydrogenase 1 mutation， over-expression of glial fibrillary acidic protein and 1p19q co-deletion. Furthermore， a high level of FEZF1 in patients with glioma acted as an independent biomarker to predict reduced survival (P = 0.026). In an in vitro experiment， FEZF1 can promote the proliferation， migration， and invasion of glioma cells and inhibit cell apoptosis by activating Akt-ERK pathway. All these findings suggest that FEZF1 acts as a key oncogene and predicts a poor prognosis in glioma.