For the past two decades, many researchers have been investigating the potential cancer-preventive and therapeutic effects of green tea. (-)-Epigallocatechin-3-O-gallate (EGCG) has been shown to be the most active and major polyphenolic compound from green tea. The mechanisms of action of EGCG have been extensively investigated. However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated. Recently, we have identified the 67-kDa laminin receptor (67LR) as a cell surface EGCG receptor that confers EGCG responsiveness to many cancer cells at physiological concentrations. This article reviews some of the reported mechanisms and possible targets for the action of EGCG. We especially focus on the current understanding of the signaling pathway for physiologically relevant EGCG through the 67LR for cancer prevention. Our data shed new light on the molecular basis for the cancer-preventive activity of EGCG in vivo and helps in the design of new strategies to prevent cancer.