Previous studies have reported that microRNA (miR)-505 exhibits important effect in human cancers. However, the regulatory mechanism of miR-505-3p/high-mobility group box 1 (HMGB1) axis is still unclear in glioma. Therefore, the regulatory mechanism of miR-505-3p/HMGB1 axis in glioma was illuminated. Expression of miR-505-3p and HMGB1 was observed by RT-qPCR. Protein expression was measured by western blot analysis. Dual luciferase assay was performed to confirm the relationship between miR-505-3p and HMGB1. The function of miR-505-3p was investigated by MTT and Transwell assays. Expression of miR-505-3p was reduced in glioma, which was related to poor clinical outcomes and prognosis in glioma patients. Moreover, overexpression of miR-505-3p suppressed proliferation, migration and invasion of glioma cells. In addition, HMGB1 was confirmed as a direct target of miR-505-3p, and miR-505-3p inhibited the development of glioma by targeting HMGB1. Furthermore, miR-505-3p blocked EMT suppressing p-AKT expression in glioma cells. In conclusion, miR-505-3p inhibited the development of glioma by targeting HMGB1 and regulating AKT expression.