Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of all head and neck cancers and is associated with high mortality rates, due to the high infiltrative potential of these tumors. Despite advances in treatment approaches, there has been no improvement in survival rates. As empiricism in the treatment of HNSCC is unlikely to improve the prognosis of HNSCC patients, understanding the pathogenesis behind the local invasion of these tumors on the cellular and molecular levels has become an important goal in the field of head and neck surgery. It is believed that the invasive growth of neoplastic cells is a deregulated form of the physiological program that occurs during the formation and patterning of an embryo, which is largely facilitated by HGF induced signaling through its receptor c-MET. This review investigates whether HGF and c-MET are deregulated in HNSCC and whether they confer an invasive potential to these tumors. It is concluded that both molecules are mis- and over-expressed in HNSCC and probably induce the program of invasive growth in HNSCC.