The review discusses the role of the miR-34 family in cancer and apoptosis, focusing on the transcription factor p53 and its regulation of microRNA expression. p53, a tumor suppressor gene, activates the expression of miR-34a and miR-34b/c, which are direct targets of p53. Ectopic expression of these microRNAs induces apoptosis, cell-cycle arrest, or senescence. In many cancers, the promoters of miR-34a and miR-34b/c are inactivated by CpG methylation. MiR-34a, located on chromosome 1p36, is commonly deleted in neuroblastomas, and its loss is associated with resistance to p53-activating chemotherapy agents. The review highlights the evidence for the role of miR-34a and miR-34b/c in the apoptotic response of normal and tumor cells, and their potential as therapeutic targets in cancer. Additionally, it explores the feedback loop between miR-34a and p53, where miR-34a targets SIRT1 mRNA, leading to increased p53 activity and further apoptosis induction. The detection of miR-34 expression may have diagnostic and prognostic value in various cancers, and restoring miR-34 function could be a therapeutic strategy.The review discusses the role of the miR-34 family in cancer and apoptosis, focusing on the transcription factor p53 and its regulation of microRNA expression. p53, a tumor suppressor gene, activates the expression of miR-34a and miR-34b/c, which are direct targets of p53. Ectopic expression of these microRNAs induces apoptosis, cell-cycle arrest, or senescence. In many cancers, the promoters of miR-34a and miR-34b/c are inactivated by CpG methylation. MiR-34a, located on chromosome 1p36, is commonly deleted in neuroblastomas, and its loss is associated with resistance to p53-activating chemotherapy agents. The review highlights the evidence for the role of miR-34a and miR-34b/c in the apoptotic response of normal and tumor cells, and their potential as therapeutic targets in cancer. Additionally, it explores the feedback loop between miR-34a and p53, where miR-34a targets SIRT1 mRNA, leading to increased p53 activity and further apoptosis induction. The detection of miR-34 expression may have diagnostic and prognostic value in various cancers, and restoring miR-34 function could be a therapeutic strategy.