Here we present a quartz crystal microbalance (QCM) sensor for the highly selective and sensitive detection of Hg ion, a toxic chemical species and a hazardous environmental contaminant. Hg ion can be quantitatively measured based on changes in the resonance frequency of QCM following mass changes on the QCM sensor surface. The high selectivity for Hg ion in this study can be obtained using a thymine-Hg-thymine pair, which is more stable than the adenine-thymine base pair in DNA. On the other hand, gold nanoparticles (AuNPs) and their size-enhancement techniques were used to amplify the QCM signals to increase the sensitivity for Hg ion. With this strategic approach, the proposed QCM sensor can be used to quantitatively analyze Hg ion with high selectivity and sensitivity. The detection limit was as low as 98.7 pM. The sensor failed to work with other metal ions at concentrations 1000-times higher than that of the Hg ion. Finally, the recovery does not exceed 10% of the original value for the detection of Hg ion in tap and bottled water. The results indicate acceptable accuracy and precision for practical applications.