The adsorption of single-stranded oligonucleotides (ssDNA) on gold nanoparticles (AuNPs) could stabilize AuNPs against aggregation even at high salt concentrations, and similar phenomena have also been observed on Au core/Pt shell nanoparticles (Au@PtNPs). Inspired by the knowledge that thymine can easily recognize melamine by forming triple H-bonds in aqueous medium, in this contribution, using polythymine-coated Au@PtNPs as the probe, we demonstrated that the responsive aggregation of polyT₅₅ stabilized Au@PtNPs could occur and therefore result in the significant inhibition of the catalysed gas-generation reaction, the decomposition of H₂O₂ to H₂O and O₂ catalyzed by Au@PtNPs. Consequently, a pressure-based signaling strategy was developed for highly sensitive and specific melamine detection not only in laboratory but also in point-of-care (POC) settings, and the correlation between the pressure change (ΔP) signal and the melamine concentration was found to be linear from 0.025 to 10.0 μM with a limit of detection of 6.4 nM, providing a convenient new alternative and new train of thought for the specific detection of melamine.