We report that GSPs inhibit the invasive potential of the OSC19 HNSCC cells through inhibition or reversal of EMT and that this GSPs-induced inhibition is accomplished through a process that involves a reduction in the levels of EGFR expression, inactivation of NF-κB and inactivation of Erk1/2. Here, EGFR is linked to head and neck squamous cell carcinoma.