The long non‑coding RNA KCNQ1OT1 is generally recognized as an oncogenic molecule in several human malignant tumors. However, to the best of our knowledge, the role of KCNQ1OT1 in glioma has not been fully investigated. The current study aimed to probe the biological function of KCNQ1OT1 in human glioma cell lines and its mechanisms. The glioma cell lines U251 and U87‑MG were used as cell models. Cell proliferation and apoptosis assays were used to measure the effects of different treatments on survival, and reverse transcription‑quantitative PCR and western blotting were used to investigate the expression profiles of key molecules. Migration and invasion assays were conducted to reveal the biological features of glioma cells. The results indicated that KCNQ1OT1 was upregulated in glioma tissues compared with adjacent tissues, which was associated with poor prognosis. Additionally, knockdown of KCNQ1OT1 in U251 and U87‑MG cells inhibited cell proliferation, migration and invasion, but had no effect on apoptosis. The effects of KCNQ1OT1 on migration and invasion were partially attributed to enhanced Yes‑associated protein (YAP) expression levels and epithelial‑mesenchymal transition (EMT) signaling. Furthermore, microRNA (miR)‑375 functioned as a link between KCNQ1OT1 and YAP in regulating cell proliferation. Finally, the KCNQ1OT1/miR‑375/YAP axis modulated cell proliferation and cell fate by affecting the modulated YAP‑mediated EMT signaling. In conclusion, the KCNQ1OT1/miR‑375/YAP axis modulated migration and invasion of glioma cells by affecting EMT signaling; thus, targeting KCNQ1OT1 may represent a promising strategy in glioma therapeutics.