Imbalanced cell death is a common phenomenon in many human diseases, including cancer. DAPK's essential function is in promoting apoptosis. DAPK interacts with stress-induced receptors through its death domain to initiate an apoptosis cascade. In addition, DAPK phosphorylates multiple cytosolic substrates and can mediate transfer of signaling pathways to the effector caspases. A series of studies demonstrated that, depending on stimuli, DAPK expression is regulated on both the transcriptional and posttranscriptional levels. Silencing of DAPK due to hypermethylation of its promoter was reported in many types of cancer. STAT3 and p52-NFkB transcription factors have been shown to down-regulate DAPK expression. In contrast, p53, C/EBP-β and Smad transcription factors bind to their specific response elements within the DAPK promoter and induce its transcription. Post-transcriptionally, DAPK undergoes alternative splicing, which results in the production of two functionally different isoforms. Moreover, miRNA 103 and miRNA 107 recently were shown to inhibit DAPK in colorectal cancer. Here we summarize our recent knowledge about transcriptional regulation of DAPK expression.