Objective To investigate the effects of hederagenin (HDG) on proliferation, migration, invasion and apoptosis of glioblastoma (GBM) cells and involved mechanism.Methods Human GBM cell lines U87, U251 and human brain glial cell line (HEB) were selected as the study subjects, and HDG 0μmol/L (or 0 mg/kg) was used as the control group.MTT, EdU staining and cell plate cloning were used to detect the effect of HDG on the proliferation of GBM cells.Trypan blue staining was used to detect GBM cell death affected by HDG.The effects of HDG on migration and invasion of GBM cells were detected by cell scratch and Transwell assay.To analyze the effects of HDG on apoptosis of GBM cells, apoptosis-related proteins Bcl-2, Bax, p53 and cleaved caspase-3 were detected by Western blot.Mitochondrial potential change was detected by JC-10 staining, and apoptotic cell count was displayed by Annexin V-FITC staining.The effect of HDG on tumor bearing in GBM was analyzed by xeno-transplantation in BALB/C mice.Results Compared with the control group (HDG0 μmol/L), HDG significantly inhibited the proliferation, migration and invasion of U87 and U251 cells, and they were dependent on the use dose of HDG.Trypan blue staining showed that HDG obviously increased death number of GBM cells.The mitochondrial potential of GBM cells was remarkedly decreased, the number of apoptotic GBM cells obviously increased, the ex-pressions of apoptosis-related proteins p53, Bax, cleaved-caspase3 were up-regulated and Bcl-2 was down-regulated by HDG in U87 and U251 cells.HDG significantly inhibited the size of subcutaneous GBM, the Ki67 positive rate of GBM cells and caused a large number of GBM cells to die in BALB/C mice.HDG had no obvious toxic effect on human HEB cells and the liver of tumor-bearing mice.Conclusion HDG can significantly inhibit the prolifera-tion, migration and invasion of GBM cells and induce the apoptosis of them.The mechanism of HDG induced apop-tosis of GBM cells may be through mitochondrial damage and regulation of p53 and Bcl-2/Bax expression.