A novel nanoparticle label capable of amplifying the electrochemical signal of DNA hybridization is fabricated by functionalizing poly(styrene-co-acrylic acid) microbeads with CdTe quantum dots. CdTe-tagged polybeads are prepared by a layer-by-layer self-assembly of the CdTe quantum dots (diameter = 3.07 nm) and polyelectrolyte on the polybeads (diameter = 323 nm). The self-assembly procedure is characterized using scanning and transmission electron microscopy, and X-ray photoelectron, infrared and photoluminescence spectroscopy. The mean quantum-dot coverage is (9.54 ± 1.2) × 103 per polybead. The enormous coverage and the unique properties of the quantum dots make the polybeads an effective candidate as a functionalized amplification platform for labelling of DNA or protein. Herein, as an example, the CdTe-tagged polybeads are attached to DNA probes specific to breast cancer by streptavidin–biotin binding to construct a DNA biosensor. The detection of the DNA hybridization process is achieved by the square-wave voltammetry of Cd2+ after the dissolution of the CdTe tags with HNO3. The efficient carrier-bead amplification platform, coupled with the highly sensitive stripping voltammetric measurement, gives rise to a detection limit of 0.52 fmol L−1 and a dynamic range spanning 5 orders of magnitude. This proposed nanoparticle label is promising, exhibits an efficient amplification performance, and opens new opportunities for ultrasensitive detection of other biorecognition events.