The most potent catechin in green tea is (-)-epigallocatechin-3-gallate [(-)EGCG], which, however, is unstable under physiological conditions. To discover more stable and more potent polyphenol proteasome inhibitors, we synthesized several novel fluoro-substituted (-)- EGCG analogs, named F-EGCG analogs, as well as their prodrug forms with all of - OH groups protected by acetate. We report that the prodrug form of one F-EGCG analog exhibited greater potency than the previously reported peracetate of (-)EGCG to inhibit proteasomal activity, suppress cell proliferation, and induce apoptosis in human leukemia Jurkat T cells, demonstrating the potential of these compounds to be developed into novel anti-cancer and cancer-preventive agents.