At present, emerging evidence shows that non-coding RNAs (ncRNAs) play crucial roles for development of multiple tumors. Amongst these ncRNAs, long non-coding RNAs (lncRNAs) play prominent roles in physiological and pathological processes. LncRNAs are RNA transcripts larger than 200 nucleotides and have been shown to serve important regulatory roles in different types of cancer via interactions with DNA, RNA and proteins. Head and neck squamous cell carcinoma (HNSCC) is one of the most malignant tumors with low survival rates in advanced stages. Recently, lncRNAs have been demonstrated to be involved in a wide range of biological processes, including proliferation, metastasis, and prognosis of HNSCC. Therefore, this review describes molecular mechanisms of up- or down-regulation of lncRNAs and expounds their functions in pathology and clinical practices in HNSCC. It also highlights their potential clinical applications as biomarkers for the diagnosis, prognosis, and treatment of HNSCC. However, studies on lncRNAs are still not comprehensive, and more investigations are needed in the future.