DNA-functionalized quantum dots (QDs) are powerful tools for biosensing and bioimaging applications. Facile labeling methods with good fluorescence properties are desirable for the development of DNA-functionalized QDs. In this article, we describe a novel and simple approach that leads to the synthesis of DNA-functionalized CdTe:Zn(2+) QDs in one step. It is the first time that DNA-functionalized QDs have been prepared using sodium tellurite as the tellurium source by a hydrothermal method. This approach will greatly reduce the synthesis time (only about 1 h) and simplify the synthesis process as well as reduce the complexity of the required experimental techniques. The as-prepared QDs exhibit high quantum yield, small size, and low toxicity. UV-vis spectra and FTIR characterization proved that the abundance of DNA on the surface of the QDs increased with the increase in the concentration of the feed DNA. Most importantly, these QDs functionalized with DNA have great potential to bind specifically to DNA, protein, and cell surface receptors.