Liquid biopsy,as an emerging minimally invasive early detection method for tumors,has shown great potential;however,several challenges limit its application in tumor diagnosis.Tetrahedral framework nucleic acids(tFNAs)have garnered significant attention in the biomedical field due to their structural stabili-ty,programmability,and superior intracellular endocytosis and tissue penetration capabilities.These properties make tFNAs an ideal candidate for constructing advanced biosensing platforms for liquid biopsy applications.tFNAs significantly enhance the binding efficiency of circulating tumor cells(CTCs),circulating tumor DNA(ctDNA),and extracellular vesicles(EVs),thereby improving the sensitivity and detection capability of the liquid biopsy biosensing platform.This review provides a comprehensive overview of tFNAs-based biosensors in the liquid biopsy field.It elaborates on the synthesis,characteristics,and applications of tFNAs in detecting CTCs,ctDNA,and EVs.Additionally,it discusses the diverse strategies and advantages of tFNAs in biosens-ing applications,highlighting how these features significantly enhance the performance and reliability of bio-sensors.Finally,this review addresses the current challenges faced by tFNAs in liquid biopsy and explores their future prospects,aiming to facilitate early screening,precise diagnosis,and integrated diagnostic-treat-ment approaches for tumors.