Long noncoding RNAs (lncRNAs) have been proved as important regulators in many diseases, including cancers. HOXA11 antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly upregulated in glioma tissue and cell lines compared with the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival and poorer prognosis than that of lower expression. Loss-of-function experiments revealed that HOXA11-AS knockdown inhibited the proliferation, induced cell cycle arrest at G0/G1 phase, and enhanced the apoptosis. Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-AS at 3-UTR, which was confirmed by luciferase reporter assay. In vitro rescue experiment assays, miR-140-5p inhibitor transfection, could reverse the function of HOXA11-AS knockdown on the proliferation, cell cycle arrest, and apoptosis. Taken together, the present study illustrates that the pathway of HOXA11-AS sponging miR-140-5p might play a vital regulating role in the development and progression of glioma.