Glioma is the most common intracranial malignant tumors, accounting for about 40% of intracranial tumors. Primary or secondary drug resistance is one of the main reasons for the failure of treatment. The oncogenic or tumor-suppressive roles of miR-634 have been revealed in different types of cancer. However, the role of miR-634 in glioma remains unknown and whether miR-634 could sensitize glioma cells to temozolomide also is unclear. Here, we aim to investigate the biological function of miR-634 and the possible mechanisms in glioma. In this study, we found that miR-634 was downregulated in glioma tissues compared with normal brain tissues, and its expression was associated with tumor size and WHO grade. Importantly, glioma patients with low miR-634 expression showed a shorter survival time than patients which had high expression of miR-634. This study also showed that miR-634 was decreased in temozolomide-resistant glioma cells, and restoration of miR-634 could sensitize the resistant cells to temozolomide by targeting CYR61 through Raf-ERK signaling. Our study provides a potential target for overcome drug resistance in glioma.