A simple and sensitive colorimetric Hg 2+ detection method is reported, based on the Hg 2+ -mediated structural switch of an unlabeled oligonucleotide strand. In the absence of Hg 2+ , the oligonucleotide strand forms a stem-loop. A G-rich sequence in the strand is partially caged in the stem-loop structure and cannot fold into a G-quadruplex. In the presence of Hg 2+ , T–Hg 2+ –T coordination chemistry leads to the formation of another stem-loop structure and the release of the G-rich sequence. The released sequence folds into a G-quadruplex, which binds hemin to form catalytically active G-quadruplex DNAzymes. This is detected as an absorbance increase in a H 2 O 2 –2,2′-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid (ABTS) reaction system using UV–vis absorption spectroscopy. This simple colorimetric sensor can detect aqueous Hg 2+ at concentrations as low as 9.2nM with high selectivity. Based on the strong binding interaction between Hg 2+ and the sulfur-containing amino acid cysteine (Cys), and the competition between Cys and a oligonucleotide for Hg 2+ , the proposed Hg 2+ -sensing system can be further exploited as a Cys-sensing method. The method has a detection limit for Cys of 19nM.