Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic. The existence of CSCs is under debate and the origin of CSCs is an active research area. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Cancer stem cells (CSCs) have been identified in head and neck squamous cell carcinoma (HNSCC). So, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease like (HNSCC).