Glioma is one of the most aggressive and lethal human cancers in central nervous system (CNS). Recent studies have identified many dysregulated microRNAs (miRNA, miR) in human glioma, which are a class of small non-coding RNA molecules. Increasing data have shown that miR-18a plays significant roles in several tumors. However, its effects on glioma are unclear. In this study, we found the elevated expression of c-Fos and miR-18a in tissues of human glioma patients and glioma cells. Then the miR-18a inhibitor or c-Fos siRNA were transfected into glioma cells line H4 to determine their effects on H4 cells. MTT assay showed that both miR-18a inhibitor and si-c-Fos suppressed the H4 cell proliferation. Transwell assay showed the reduced cell migration by miR-18a inhibitor and si-c-Fos in H4 cells. The increased level of H4 cells apoptosis by miR-18a inhibitor and si-c-Fos was also determined. Moreover, knockout of c-Fos decreased the miR-18a level, while miR-18a inhibitor reduced the c-Fos level in H4 cells. Added with the results of ChIP assay, this report showed a positive feedback between c-Fos and miR-18a. Finally, luciferase assay showed that HMBOX1 was directly targeted by miR-18a in H4 cells, and the HMBOX1 siRNA reversed the effects of miR-18a inhibitor on cell proliferation, migration and apoptosis of H4 cells. In conclusion, our study determine that c-Fos/miR-18a feedback loop promotes the tumor growth of gliomas by HMBOX1, providing important clues for understanding the key roles of transcription factor mediated mRNA-miRNA functional network in the regulation of gliomas.