Long non-coding RNAs (lncRNAs) play a critical role in several human diseases, particularly in solid tumors. Specific lncRNAs are effective biological molecular markers for diagnosing diseases and determining patient prognosis for designing molecularly targeted therapies. HOTAIR is reportedly involved in several physiological emerging processes in solid tumor, such as unlocking phenotypic plasticity, polymorphic microbiome, and cellular senescence, and has been implicated in tumorigenesis and progression. This review summarizes the relationship between the levels of expression, biological features, clinical symptoms, and regulatory mechanisms of HOTAIR action in solid cancers and discusses the clinical applicability of HOTAIR as a biomarker for predicting risk, diagnosis, prognosis, and designing targeted therapy for cancer.