With the rapid development of nanotechnology and its associated waste stream, public concern is growing over the potential toxicity exposure to heavy metal ions poses to the human body and the environment. Herein, we report an extremely sensitive Kelvin probe force microscopy (KPFM)-based platform for detecting nanotoxic materials (e.g. Ag+) accomplished by probing the integrated surface potential differences of a single gold nanoparticle on which an interaction between probe DNA and target DNA occurs. This interaction can amplify the surface potential of the nanoparticle owing to the coordination bond mediated by Ag+ (cytosine-Ag+-cytosine base pairs). Interestingly, compared with conventional methods, this platform is capable of extremely sensitive Ag+ detection (∼1 fM) in a remarkably wide-range (1 fM to 1 μM). Furthermore, this platform enables Ag+ detection in a practical sample (general drinking water), and this KPFM-based technique may have the potential to detect other toxic heavy metal ions and single nucleotide polymorphisms by designing specific DNA sequences.