MicroRNAs (miRNAs) are endogenously small non-coding RNAs which are key post-transcriptional regulators of gene expression. Deregulation of miRNAs is common in human tumorigenesis. We report that miRNA-205 is significantly down-regulated in glioma cell lines and tissue specimens. Ectopic expression of miRNA-205 induces apoptosis, cell cycle arrest, impairs cell viability, clonability and invasive properties of glioma cells. We further demonstrate that miRNA-205 can specifically suppress expression of VEGF-A by directly interacting with the putative miRNA-205 binding site at the 3'-UTR. Identification of VEGF-A as a direct target for miRNA-205 may imply that miRNA-205 is a novel target for glioma therapy. Taken together, the present study for the first time provides evidence that miRNA-205 is a glioma-specific tumor suppressor by targeting VEGF-A.