P53 protein regulates cell responses to DNA damage to keep genomic stability by transactivation and trans-repression of its downstream target genes. P53 protein also has activators, inactivators, or co-factors via interaction with other proteins. Both the p53-regulated genes and interacted proteins form a huge network. As tumors usually escape from proliferating controls by means of accumulation of genetic alterations, p53 is one of the most important tumor suppressor genes that can be targeted for diagnosis, prognosis, and therapeutic intervention. Reviewing the p53-network is of great importance. In this review, we are focusing on cancer-related p53 downstream-regulated genes. Various methods dealing with the discovery of p53-regulated genes by the detection of gene expression have been applied. Recently high throughput functional genomics methods, such as DNA microarray, serial analysis of gene expression (SAGE), differential display, and protein two-dimensional gel electrophoresis, have provided a wealth of information on the dynamics of cell context responses. Hundreds of genes have been discovered whose transcriptions are regulated by p53 protein. They were grouped, based on their functions, into sub-classes including cell-cycle regulation, DNA repair, angiogenesis, metastasis, and multidrug resistance. P53 plays a pivotal role in keeping genomic stability and tumor suppression. The deeper we investigate the cell responses as mediated by p53, the more complex p53-network becomes. However, understanding p53-network, offers great opportunities to develop more sensitive and accurate diagnostic/prognostic tools, as well as more efficient therapies for cancer.