Abstract: Glioma is the most common primary tumor of the central nervous system, with glioblastoma multiforme of World Health Organization grade Ⅳ exhibiting the highest malignancy and worst prognosis. Long non-coding RNA (lncRNA) is a type of regulatory RNA without protein-coding ability, which can promote the malignant phenotypic evolution of glioma cells and induce therapeutic resistance by reprogramming glycolytic metabolism, playing a crucial role in the malignant progression and prognosis of glioma. This paper mainly introduced the role of lncRNA in regulating the biological behavior of glioma cells and aerobic glycolysis, and proposed a new paradigm of combined therapy based on the aerobic glycolysis metabolism-epigenetic network, providing new ideas for the discovery of diagnostic biomarkers and the development of novel therapeutic strategies for glioma.