p202, an interferon (IFN) inducible protein, is a phosphonuclear protein involved in the regulation of cell cycle, apoptosis, and differentiation. E2F1 belongs to the E2F family of proteins that are important cell cycle regulators in promoting cell growth. On the other hand, the deregulated expression of E2F1 also triggers apoptosis independent of p53 status. It has been well documented that p202 is able to inhibit cell growth by binding to E2F1 and abolishing the E2F1-mediated transcriptional activation of S-phase genes. However, it is not known whether E2F1-mediated apoptosis can be counteracted by p202 expression. Here, we show that E2F1-mediated apoptosis induced by the infection of an E2F1-expressing adenoviral vector (Ad-E2F1) was greatly diminished in p202-expressing prostate cancer cells. The E2F1-mediated caspase-3 activation was also reduced in p202-expressing cells infected with Ad-E2F1. Since caspase-3 is one of the E2F1 transcriptional targets, this result is consistent with the ability of p202 to inhibit the transcriptional activity of E2F1. Therefore, our results suggest a possible link between the IFN and E2F pathways in regulating apoptosis.