Glioblastoma is a highly aggressive brain tumor and is considered to be the most common primary one. Recurrence after treatment is a major problem. The recurrence of GBM is related to different cellular mechanisms and molecular signaling. Therapies to prolong survival are not completely effective. Epigenetics and non-coding genetic elements play a crucial role in gliomagenesis. Non-coding RNAs are novel regulatory RNAs that play key roles in different physiological processes such as gene regulation, cell differentiation, and proliferation. Interestingly, some LncRNAs have a tumor suppressor role while others are oncogenic. In this review article, we are going to illustrate the role of a well-known lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in glioma and highlight the possible functions in glioma in both pre-clinical and clinically evident studies.