Head and neck cancer (HNC), a common malignancy worldwide, is associated with high morbidity and mortality rates. Squamous cell carcinoma is the most common HNC type, followed by salivary gland carcinomas, head and neck sarcomas, and lymphomas. The microenvironment of HNCs comprises various cells that regulate tumor development. Recent studies have reported that the tumor microenvironment, which modulates cancer progression, regulates cancer treatment response. However, the presence of different types of stromal cells in cancers is a major challenge to elucidate the role of individual cells in tumor progression. The role of mesenchymal stromal cells (MSCs), which are a component of the tumor microenvironment, in HNC is unclear. The major impediment for characterizing the role of MSCs in cancer progression is the lack of MSC-specific markers and their phenotypic similarity with stromal cells. This review aimed to summarize the latest findings on the role of MSCs in the progression of HNC to improve our understanding of HNC pathophysiology.