This review primarily summarizes the clinical applications of deoxyribonuclease I (DNase I). Human DNase I exhibits polymorphism at both the protein and DNA level, and thus is potentially one of the best biochemical markers for forensic practice. Clinically, DNase I activity in serum can be used as a novel diagnostic marker for the early detection of acute myocardial infarction and transient myocardial ischemia. Furthermore, the DNase I gene is considered to be one of the susceptibility genes for gastric and colorectal carcinoma, and myocardial infarction. Over the last decade since the discovery of the utility of its genetic polymorphism for forensic purposes, research on DNase I has expanded into clinical applications.