The mortality rate of patients with glioma is increasing worldwide per annum. This is attributed to the poor disease prognosis, most notably for high-grade gliomas (grade III and IV), which does not improve the overall patient survival. The dysregulation of microRNA (miRNA/miR)-124-3p is found in a variety of tumors. However, the association between miR-124-3p expression and its target genes in glioma has not been thoroughly elucidated. The present study aimed to explore the possible effects of miR-124-3p and its proved target, Ras homology Growth-related (RhoG), on the oncogenic events associated with glioblastoma multiforme (GBM) development. The data demonstrated an inverse association between miR-124-3p and RhoG expression levels during GBM progression in GBM tissues and cells. U87 and U251 cells were employed for the in vitro assays. Luciferase reporter assays revealed that miR-124-3p interacted with RhoG at the RhoG 3 ' untranslated region and inhibited RhoG expression in GBM cells. Functionally, enriched miR-124-3p repressed RhoG transcription and suppressed GBM cell proliferation and migration, promoting apoptosis and altering the expression or activity of the apoptosis-related proteins of GBM cells. By contrast, the inhibition of miR-124-3p in GBM cells upregulated RhoG levels and promoted the proliferation of GBM cells. The knock down of RhoG expression by specific small interfering RNA sequences partially neutralized the effects induced by the miR-124-3p inhibitor. In conclusion, the present study demonstrated the crucial effects of miR-124-3p on the development and deterioration of GBM by targeting RhoG.