The aim of this study was to develop a highly specific electrochemical DNA sensor using functionalized lead sulphide (PbS) quantum dots for hepatitis E virus genotype 3 (HEV3) DNA target detection. Functionalized-PbS quantum dots (QDs) were used as an electrochemical label for the detection of HEV3-DNA target by the technique of square wave anodic stripping voltammetry (SWASV). The functionalized-PbS quantum dots were characterized by UV-vis, FTIR, XRD, TEM and zeta potential techniques. As-prepared, functionalized-PbS quantum dots have an average size of 4.15 ± 1.35 nm. The detection platform exhibited LOD and LOQ values of 1.23 fM and 2.11 fM, respectively. HEV3-DNA target spiked serum is also reported.Graphical abstract.