Long non-coding RNA ( lncRNA) X inactivate-specific transcript (XIST) acts as an important regulator in tumor progression. However, its expression and the underlying mechanism in glioma remain unclear. The aim of this study was to explore the potential function of XIST in glioma progression. In the present study, our data showed that the expression of XIST was significantly up-regulated in glioma tissues and enhanced the proliferation of glioma cells. The expression of miR-137 was significantly decreased in glioma tissues. Further correlation analysis demonstrated that there was a negative correlation between XIST expression and miR-137 expression. Bioinformatics prediction and luciferase reporter assays demonstrated that miR-137 could directly bind to XIST and negatively regulated the expression of miR-137. Additionally, our data further showed that XIST could up-regulate the expression of miR-137 targeted gene Rac1 through acting as an endogenous sponge of miR-137. In addition, we found that Rac1 inhibition or miR-137 overexpression could suppress glioma cells proliferation induced by XIST overexpression. Thus, a novel XIST-miR-137-Rac1 pathway regulatory axis in glioma pathogenesis was revealed in the present study. Overall, our study indicated that XIST could be a potential therapeutic target in the treatment of glioma.