It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients.