Hypoxia-inducible factor 1α (HIF-1α), which is regulated oxygen-dependently, transactivates numerous genes essential for cellular adaptation to hypoxia. HIF-1α expression is regulated at multiple steps from transcription to protein degradation. Moreover, the stability of HIF-1α protein has been known to be determined by posttranslational modifications such as ubiquitination, sumoylation, neddylation, and acetylation, but the HIF-1α regulation by methylation has not been reported. Protein methylation at arginine residues is an essential process to regulate gene expressions and signal transductions, and is catalyzed by PRMT enzymes. While testing which PRMT isoforms participate in the HIF-1 signaling pathway, we found that one of PRMTs modulates HIF-1α expression under hypoxia. When the PRMT was knocked-down in glioblastoma cells, HIF-1α was expressed even under normoxia and further induced under hypoxia. The transcriptional activity of HIF-1 was evaluated in reporter systems using EPO enhancer-luciferase or VEGF promoter-luciferase vector, and the HIF-1-driven gene expressions were checked by RT-qPCR. These assays demonstrated that functional HIF-1 was induced by PRMT knock-down. We next studied the mechanism of the HIF-1α induction, and found that HIF-1α was induced at the translational level through activated PI3K/Akt/mTOR signaling. Based on these findings, we propose that the PRMT negatively controls de novo synthesis of HIF-1α protein regardless of oxygen level. Given many literatures supporting the cancer promoting action of HIF-1α, the PRMT could be a potential target for cancer therapy.