Abstract: Malignant tumor is one of the main causes of human death. Early diagnosis and precise treatment can significantly improve the prognosis of cancer patients. With the rapid development of liquid biopsy technology, new tumor markers such as circulating tumor cells, exosomes, circulating tumor DNA and circulating free DNA have been found to have become a research detection with tremendous potential for clinical application, providing more precise detection methods for tumor diagnosis and treatment. Compared with cell free nuclear DNA, cell free mitochondrial DNA (cf-mtDNA) has such characteristics as small genome, multiple copy numbers and high mutation frequency. The unique advantages of cf-mtDNA in tumor diagnosis and treatment have made it more attractive with a promising application prospect. This article reviews the characteristics, detection techniques, and analytical indicators of circulating cf-mtDNA, as well as the application value of cf-mtDNA in early diagnosis, precision medicine, efficacy monitoring, and prognosis prediction.