This article reviews two main topics: (1) the synergistic effects of multiple treatments with green tea catechin and (2) the direct binding of (-)-epigallocatechin gallate (EGCG) to both DNA and RNA molecules. Japanese drink green tea throughout the day, so we studied whether multiple treatments of cells with EGCG would enhance the expression of apoptosis-related genes, such as growth arrest and DNA damage-inducible gene (GADD153) and cyclin-dependent kinase inhibitor gene (p21(waf1)): The results suggest that the synergistic enhancement of both GADD153 and p21(waf1) gene expressions by multiple treatments plays a significant role in human cancer prevention with green tea beverage. Our previous observation-that nucleic acids extracted from catechin-treated cells are colored-allowed us to speculate that catechins directly interact with nucleic acids. Surface plasmon resonance assay (Biacore) indicated that four catechins, EGCG, (-)-epicatechin gallate (ECG), (+)-gallocatechin gallate (GCG), and (+)-catechin gallate (CG), bound to DNA oligomers. Cold spray ionization mass spectrometry (CSI-MS) analysis showed that one to three EGCG molecules bound to single-stranded 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded AG:CT oligomers of various nucleotide lengths. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects double-stranded DNA oligomers from double-stranded melting into single-stranded DNA. We assume that catechins accumulate in both double-stranded DNA and RNA molecules through multiple administrations of green tea beverage in in vivo, and that the accumulated green tea catechins play a significant role for human cancer prevention.