Body fluid biopsy exhibits significant promise in prenatal diagnostics,post-organ transplantation immune rejection monitoring,early tumor detection,and liver diseases due to its distinct advantages over conventional invasive ex-aminations.In the realm of liver diseases,circulating-free DNA not only mirrors hepatic function but potentially participates in the pathophysiological cascades of inflammation and coagulation alterations.The unique fragments within free DNA,cou-pled with methylation analysis,contribute to the early diagnosis of tumors and provide guidance for treatment strategies.Following organ transplantation,circulating-free DNA emerges as a pivotal marker for immune rejection reaction surveillance,offering a novel vantage point for scrutinizing rejection mechanisms.This article reviews the sources,extraction methods,and detection methods of free DNA,and the progress of its research application in liver transplantation,hepatocellular carci-noma,and liver failure.