Emerging evidence suggests that long non-coding RNAs (lncRNAs) may be involved in modulating various aspects of tumor biology and serve as potential therapeutic targets as well as novel biomarkers in the treatment of glioma. The present study investigated the role of lncRNA, Prader Willi/Angelman region RNA 5 (PAR5; also known as PWAR5), in glioma and its clinical significance in glioma cases. The expression levels of PAR5 were determined in clinical samples and U87, U251 cells using real-time reverse transcription quantitative polymerase chain reaction (qRT-PCR) analysis. The effects of PAR5 on cell proliferation, migration and invasion were determined using in vitro assays. RNA immunoprecipitation (RIP) and RNA pull-down assays, as well as the evauation of the expression of various oncogenes were carried out to reveal the underlying mechanisms. We found that PAR5 was significantly downregulated in glioma tissues and cell lines. Furthermore, PAR5 expression was negatively correlated with tumor size, World Health Organization (WHO) grade and Karnofsky performance score (KPS). Patients with low PAR5 expression in tumors had a worse overall survival compared to those with higher expression. Finally, in vitro restoration of PAR5 expression inhibited human glioma cell proliferation, invasion and migration by binding to EZH2 and regulating oncogene expression. This finding may provide a therapeutic approach for the future treatment of glioma.