Our results show that treatment of HNSCC cell lines from different sub-sites with GSPs results in inhibition of cell proliferation/growth and induction of apoptosis and that GSPs-induced inhibition of HNSCC cell growth is mediated through a process that involves a reduction in the levels of EGFR and reactivation of cyclin-dependent kinase inhibitory (Cdki) proteins (Cip1/p21 and Kip1/p27) in HNSCC cells in vitro and in vivo models. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.