Glioma is the most aggressive and malignant type of primary intracranial tumor. In recent decades, despite the rapid development of modern surgery and therapeutic strategies available for brain tumors, the prognosis of glioma remains poor and the median survival time is <15 months. In this study, we found that the levels of miRNA-320a were significantly decreased in patients with glioma, and that elevated miRNA-320a expression was associated with a better prognosis. In addition, aquaporin 4 (AQP4) was identified as a direct target of miRNA-320a. Overexpression of miRNA-320a led to the inhibition of cell invasion and migration via targeting of AQP4. Therefore, our results suggested that miRNA-320a could suppress the aggressive capacity of tumors by targeting AQP4, and that miRNA-320a could serve as a new effective therapeutic target for glioma surgical and therapeutic strategies.