This observation demonstrates that the efficacy of C2 on CSCs is largely through its inhibitory effect on EGF/EGFR signal pathway and C2 not only effectively inhibited the in vivo growth of transplanted HNSCC but also blocked the activation of EGFR signal and resulted in loss of expression of multiple CSC markers in HNSCC. Here, EGF is linked to head and neck squamous cell carcinoma.