In this short paper, we discuss the potential of green tea extract, (-)-epigallocatechin-3-galate (EGCG) in HNSCC chemoprevention, focusing on two aspects that are provided recently: (1) evidence of clinical efficacy and (2) unique biological effects on “lipid raft” that emerged as an important platform of numerous biophysical functions, for example, receptor tyrosin kinases (RTKs) signalings including epidermal growth factor receptor (EGFR), which play critical roles in HNSCC carcinogenesis. Here, EGFR is linked to head and neck squamous cell carcinoma.