In recent years, microRNAs (miRNAs) have been identified as mediators of tumour suppression and stress responses exerted by the p53 tumour suppressor. p53-regulated miRNAs contribute to tumour suppression by controlling the expression of central components of multiple processes, including cell cycle progression, epithelial–mesenchymal transition, stemness, metabolism, cell survival and angiogenesis. The expression and activity of p53 itself is also under the control of miRNAs. Finally, genetic and epigenetic alterations identified in the p53–miRNA network indicate that these pathways are important for the initiation and progression of tumours. In the future, knowledge about the p53–miRNA network may be able to be exploited for diagnostic and therapeutic approaches in cancer prevention and treatment.