The long non-coding RNA HOTAIR is overexpressed in many cancers and is associated with several cancer-promoting effects, including increased cell proliferation, migration and treatment resistance. HOTAIR levels correlate with tumor stage, lymph node metastasis and overall survival in patients with various types of cancer. This highlights the potential uses of HOTAIR, including early cancer detection, predicting patient outcome, identifying high-risk individuals and assisting in therapy selection and monitoring. The aim of this review is to provide a comprehensive summary of the research progress, molecular mechanisms and clinical significance of HOTAIR in various human cancers. In addition, the clinical applications of HOTAIR, such as targeted therapy, radiotherapy, chemotherapy and immunotherapy, are discussed, and relevant information on the potential future advances of HOTAIR in cancer research is provided.