Tumor suppressor p73 plays an important role in the regulation of DNA damage response. E2F-1 acts as a transcriptional regulator for p73. In the present study, we have found that acetylation of E2F-1 has a critical role in the E2F-1-mediated transactivation of p73. In response to adriamycin (ADR), p73 was stabilized in HeLa cells and the expression levels of its target genes increased in association with an induction of apoptosis. Of note, E2F-1 and several its target genes were transactivated in response to ADR, whereas p73 mRNA level remained unchanged. Immunoprecipitation analysis revealed that ADR has a marginal effect on acetylation status of E2F-1. Intriguingly, acetylation level of E2F-1 remarkably increased in the presence of trichostatin A (TSA) and thereby inducing the expression level of p73 mRNA. Taken together, our present findings suggest that acetylation status of E2F-1 contributes to the selective activation of its target genes.