BACKGROUND: To investigate the influences of HOX transcript antisense ribonucleic acid (HOTAIR) on the proliferation and apoptosis of glioblastoma cells by targeting micro RNA (miR)-219. OBJECTIVE: With glioblastoma cell line U87 as the object, the changes in expression levels of HOTAIR and miR-219 in each group were detected via quantitative real-time polymerase chain reaction (qRT-PCR) after HOTAIR in U87 cell lines was knocked down using small interfering RNA (siRNA). Then the cell proliferation in each group was determined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was applied to detect the cell apoptosis, and Western blotting assay was adopted to measure the changes in protein levels of Cyclin D1 and Bcl-2-associated X protein (Bax). After miR-219 knockdown with siRNA, the changes in expression levels of HOTAIR and miR-219 in each group were examined through qRT-PCR, and the cell proliferation was tested by CCK-8 assay. RESULTS: After interference inHOTAIR using siRNA, compared with those in control group, the RNA expression level of HOTAIR was decreased remarkably (p < 0.05), the RNA expression level of miR-219 was increased notably (p < 0.05), the cell proliferation rate was inhibited evidently (p < 0.05), the apoptosis rate was enhanced obviously (p < 0.05), the protein expression level of Cyclin D1 declined markedly (p < 0.05), and the protein expression level of Bax rose distinctly (p < 0.05) in HOTAIR-siRNA group. After miR-219 knockdown with siRNA, the cell proliferation rate was raised remarkably (p < 0.05), but there was no significant change in the RNA expression level of HOTAIR (p > 0.05). CONCLUSION: HOTAIR can repress the proliferation and promote the apoptosis of glioblastoma cells by targeting miR-219.