In mammals, one of the key regulators necessary for responding to genotoxic stress is the p53 transcription factor. p53 is the single most commonly mutated tumor suppressor gene in human cancers . Here we report the identification of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosuppression technology, we show that C. elegans p53 (cep-1) is required for DNA damage-induced apoptosis in the C. elegans germline. However, cep-1 RNAi does not affect programmed cell death occurring during worm development and physiological (radiation-independent) germ cell death. The DNA binding domain of CEP-1 is related to vertebrate p53 members and possesses the conserved residues most frequently mutated in human tumors. Consistent with this, CEP-1 acts as a transcription factor and is able to activate a transcriptional reporter containing consensus human p53 binding sites. Our data support the notion that p53-mediated transcriptional regulation is part of an ancestral pathway mediating DNA damage-induced apoptosis and reveals C. elegans as a genetically tractable model organism for studying the p53 apoptotic pathway.