Nogo receptor (NgR) has been shown to inhibit the migration and invasion of human glioma cells. However, little is known regarding the regulatory mechanisms of NgR in glioblastoma multiforme (GBM). In this study, we propose a novel mechanism that regulates the maturation process of NgR through an interaction with vimentin. The inhibition of TGFβ1 activity by LY2109761 attenuated the migration/invasion of GBM cells by upregulating cell-surface NgR. Conversely, the treatment of GBM cells with TGFβ1 suppressed NgR maturation. We showed that NgR and vimentin interact, which could be a possible mechanism for the suppression of NgR maturation. The knockdown of vimentin suppressed the migration/invasion of GBM cells through the increased maturation of NgR. Finally, TCGA (The Cancer Genome Atlas) analysis also supported the association of NgR and vimentin. The maturation of NgR is regulated by the interaction of vimentin and NgR, which attenuates the invasive activity of GBM, and might be a potential therapeutic target for brain cancer.