The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.