MicroRNAs (miRs) have been found to play promoting or suppressive roles in different human cancers. However, the exact regulatory mechanism of miR-30b in glioblastoma remains unknown. Here we have shown that the expression of miR-30b is significantly increased in glioblastoma tissues and cell lines. Moreover, a high expression of miR-30b is significantly associated with a shorter survival time for glioblastoma patients. Knockdown of miR-30b caused a significant reduction in the proliferation, migration, and invasion of U87 and A172 cells. Proline-rich transmembrane protein 2 (PRRT2) was further identified as a novel target gene of miR-30b, and its protein expression is negatively regulated by miR-30b in U87 and A172 cells. Furthermore, PRRT2 is significantly downregulated in glioblastoma tissues and cell lines, and we found an inverse correlation between miR-30b and PRRT2 expression in glioblastoma tissues. In addition, inhibition of PRRT2 reversed the suppressive effect of miR-30b downregulation on the malignant phenotypes of U87 and A172 cells. Accordingly, we demonstrated that miR-30b promotes glioblastoma cell proliferation, migration, and invasion via targeting PRRT2. Therefore, miR-30b may be used as a promising therapeutic target for glioblastoma.