Abstract: Liquid biopsy technology provides a non⁃invasive approach for tumor diagnosis and dynamic monitoring by analyzing biomarkers present in body fluids， including circulating tumor cells， extracellular vesicles， and circulating cell⁃free DNA (cfDNA). Urinary cfDNA has demonstrated significant potential in the diagnosis of malignant tumors， owing to its non⁃invasive sampling and the feasibility of repeated acquisition. Emerging biomarkers， such as DNA mutation markers， copy number variations， epigenetic modifications， fragmentomic features， and cell⁃free mitochondrial DNA， have the potential to significantly enhance the early detection rates of urological cancers. These biomarkers can be utilized in the screening of non⁃urological malignancies， including lung cancer and endometrial cancer. The integration of combined analyses can further augment diagnostic efficiency. This article provides a comprehensive  review of  recent advancements in the application of urinary cfDNA for tumor diagnosis， with a particular emphasis on the diagnostic efficacy of various molecular markers and their potential for cross⁃system cancer detection. It also investigates the current challenges in clinical applications， with the ultimate objective of advancing the clinical translation of urine cfDNA detection technology and enhance the accuracy of non⁃invasive diagnostic methodologies for tumor detection.

Key words: Liquid biopsy, Cell?free DNA (cfDNA), Urine, Malignant tumors, Tumor diagnosis