Objective To observe the effect of miR-328-3p on the growth and apoptosis of glioma cells, and explore the role and mechanism of the miR-328-3p-Akt/ mTOR axis in inhibition of glioma cell growth by triptolide using U251 cells and a xenograft model in nude mice. Methods miR-328-3p overexpression were induced after treatment of with triptolide in U251 cells. qRT-PCR, CCK-8, colony formation assays, flow cytometry, and Western Blot were performed to assess the role of miR-328-3p in inhibition of U251 cells by triptolide. A xenotransplanted tumor model was established with stable miR-328-3p expression to verify the role of miR-328-3p in inhibition of glioma cells by triptolide using qRT-PCR and small animal imaging in vivo. Results miR-328-3p expression in glioma cells and tissues was decreased, and its expression level was positively correlated to the overall survival rate of patients with primary and recurrent glioma. the Akt/ mTOR signaling pathway. Conclusions miR-328-3p is a tumor suppressor gene in glioma. Triptolide promotes apoptosis of glioma cells, inhibits activation of the Akt/ mTOR signal pathway, and inhibits glioma cell growth through miR-328-3p.