Cancer-preventive effects of tea polyphenols, especially epigallocatechin-3-gallate (EGCG), have been demonstrated by epidemiological, preclinical, and clinical studies. Green tea polyphenols such as EGCG have the potential to affect multiple biological pathways, including gene expression, growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, and the ubiquitin/proteasome degradation pathway. Therefore, identification of the molecular targets of EGCG should greatly facilitate a better understanding of the mechanisms underlying its anticancer and cancer-preventive activities. Performing structure-activity relationship (SAR) studies could also greatly enhance the discovery of novel tea polyphenol analogs as potential anticancer and cancer-preventive agents. In this chapter, we review the relevant literature as it relates to the effects of natural and synthetic green tea polyphenols and EGCG analogs on human cancer cells and their potential molecular targets as well as their antitumor effects. We also discuss the implications of green tea polyphenols in cancer prevention.