Recent efforts have revealed that numerous oncogenic lncRNAs have been found play pivotal role in Glioma progression while there is little know about anti-oncogenic lncRNAs in Glioma. In current study, we found a HMGB1 regulated IncRNA, Linc00320, is significantly decreased in Glioma malignant tissues and its low expression predicts poor prognosis. Moreover, we found that the nucleus localized Linc00320 inhibits Glioma cell proliferation both in vitro and in vivo. In addition, we found that Linc00320 binds to beta-catenin and inhibits the activity of Wnt/beta-catenin signaling by disrupting beta-catenin binds to TCF4 in Glioma cells. Taken together, we firstly demonstrated the tumor suppressive lncRNA, Linc00320, is down-regulated in Glioma tissues and inhibits Glioma cell proliferation by restraining Wnt/beta-catenin signaling through segregating beta-catenin and TCF4 and revealed the novel HMGB1/Linc00320/beta-catenin axis in Glioma progression. (C) 2018 Elsevier Inc. All rights reserved.