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The aim of the present study was to investigate the radiosensitizing effects of homeobox (HOX) transcript antisense RNA (HOTAIR) long non-coding RNA on breast cancer tumor cells and examine the underlying mechanisms. Recombinant plasmid vectors containing HOTAIR gene were constructed and MDA-MB231 cells were transfected with these plasmids using liposomes. The cells were treated with radiation and cell apoptosis, proliferation, and double-stranded DNA breaks were examined. HOXD10, phosphorylated AKT (p-AKT) and p-BAD expression levels were measured using western blot analysis. The results showed a higher expression of HOTAIR in advanced tumor cells. HOTAIR efficiently enhanced radioresistance in MDA-MB231 breast cancer cells and accelerated proliferation through the Akt pathway by targeting HOXD10. In conclusion, the findings demonstrated that HOTAIR gene is a valid therapeutic target for the reversal of radiotherapy resistance in breast cancer. [ABSTRACT FROM AUTHOR]