p53 tumor suppressor has been widely recognized as the "Guardian of the Genome", reflecting its importance in ensuring the proper functioning of the cell. It is well-known for its function as a transcription factor, capable of mediating both transcriptional activation and repression, which brings about many cellular outcomes such as cell cycle arrest, apoptosis, cellular senescence and DNA repair. The canonical p53 response element (p53RE), which contains two repeats of a decamer motif "RRRCWWGYYY" separated by a spacer of 0 to 13 base-pairs, has been characterized as the regulatory region on the target genes that p53 binds for transcriptional activation. It was thought that p53 generally represses genes that lack this canonical p53RE, presumably through the sequestration of basal transcriptional machinery components or transcription activators. However, characterization of individual genes as well as genome-wide studies utilizing gene expression profiling and chromatin immunoprecipitation uncovered a large number of potential p53-repressed targets. Taken together, there appears to be multiple modes of gene repression by p53 with some being mediated through direct binding of p53 to DNA. The aim of this review is to assess the evidence of p53 mediated transcriptional repression and discuss its role in cellular function.