Abstract. The mitogen-activated protein kinase (MAPK) signaling pathway is associated with tumor cell proliferation, differentiation, apoptosis, angiogenesis, invasion and metastasis. The present review assesses the involvement of the MAPK signaling pathway in oral cancer progression and invasion based on analysis of individual sub-pathways and their mechanisms of action. The regulation of this pathway for targeted oral cancer therapy is explored and the challenges confronting this, as well as corresponding potential solutions, are discussed. Exploring this pathway with an emphasis on its components, subfamilies, sub-pathways, interactions with other pathways and clinical practice modes may improve oral cancer treatment.