Heavy metal ion pollution poses severe risks in human health and the environment. Driven by the need to detect trace amounts of mercury, this article demonstrates, for the first time, that silver/mercury amalgamation, combining with DNA-protected silver nanoparticles (AgNPs), can be used for rapid, easy and reliable screening of Hg(2+) ions with high sensitivity and selectivity over competing analytes. In our proposed approach, Hg(2+) detection is achieved by reducing the mercury species to elemental mercury, silver atoms were chosen as the mercury atoms' acceptors by forming Ag/Hg amalgam. To signal fluorescently this silver amalgamation event, a FAM-labeled ssDNA was employed as the signal reporter. AgNPs were grown on the DNA strand that resulted in greatly quenching the FAM fluorescence. Formation of Ag/Hg amalgam suppresses AgNPs growth on the DNA, leading to fluorescence signal increase relative to the fluorescence without Hg(2+) ions, as well as marked by fluorescence quenching. This FAM fluorescence enhancement can be used for detection of Hg(2+) at the a few nanomolar level. Moreover, due to excellent specificity of silver amalgamation with mercury, the sensing system is highly selective for Hg(2+) and does not respond to other metal ions with up to millimolar concentration levels. This sensor is successfully applied to determination of Hg(2+) in tap water, spring water and river water samples. The results shown herein have important implications in the development of new fluorescent sensors for the fast, easy, and selective detection and quantification of Hg(2+) in environmental and biological samples.