This paper reported that the peroxidase-like activity of DNA–Ag/Pt nanoclusters (NCs) can be inhibited selectively by Hg²⁺. The interaction between Hg²⁺ and the DNA–Ag/Pt NCs was discussed through characterization by TEM, DLS and XPS, etc. It was found that the integration of both Hg⁰ and Hg²⁺ to the DNA–Ag/Pt NCs resulted in the DNA–Ag/Pt NCs aggregation and the decrease of Pt²⁺ content on the DNA–Ag/Pt NCs surface, which finally impaired their catalytic activity. Based on the above mechanism, a colorimetric detection for Hg²⁺ was developed with a detection limit (LOD) of 5.0 nM and a linear range from 10 nM to 200 nM. The method was highly selective toward Hg²⁺ over other common metal ions, low-cost and simple, which facilitated the application of detecting Hg²⁺ in tap water.