The most frequent malignant tumor of the head and neck is head and neck squamous cell carcinoma (HNSCC), which has a high frequency, a poor prognosis in the late stages, and subpar therapeutic results. As a result, early HNSCC diagnosis and treatment are urgently needed; however, there are no good diagnostic biomarkers or efficient therapeutic targets at this time. The long-stranded non-coding RNA HOTAIR may be important in the pathogenesis of cancer, according to recent research. By interactions with DNA, RNA, and proteins, it has been demonstrated that HOTAIR, a >200 nucleotide RNA transcript, plays a role in the biological processes of many types of tumor cells, including proliferation, metastasis, and prognosis of HNSCC. Hence, this review discusses HOTAIR’s function and molecular mechanisms in HNSCC.