Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play key roles in tumor initiation and progression. However, the function of lncRNA ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion. Importantly, we further confirmed that epithelial–mesenchymal transition (EMT) and the Notch signaling pathway was inactivated in the glioma cells after ZFAS1 knockdown. Thus, our findings indicated that ZFAS1 could exhibit a tumor oncogenic role in glioma progression by regulating EMT and Notch signaling pathway. LncRNA ZFAS1 might serve as a therapeutic target for the treatment of glioma patients.