Induction of apoptosis by green tea polyphenols has been observed in various tumor cell systems, but whether green tea polyphenol-induced apoptosis requires caspase 3 for execution has not been confirmed. We previously reported that green tea polyphenol-induced apoptosis involved Apaf-1 accumulation and caspase 3 activation in the cytosol. In the current study, tumor cells either with deleted caspase 3 gene or expressing wild-type caspase 3 were treated with increasing concentrations of green tea polyphenol(s), followed by morphological analysis and caspase 3 activity assay. The caspase 3 null parental cell line was further examined in comparison with a well-characterized, caspase 3 wild type oral carcinoma cell line by MTT assay and BrdU incorporation assay. The results demonstrated that, while the mitochondrial function gradually declined to insignificant levels, caspase 3 null cells did not undergo apoptosis, which suggested that green tea polyphenol-induced apoptosis is a mitochondria-targeted, caspase 3-executed mechanism.