In this work, we synthesized gold nanoclusters within a Zirconium-based metal-organic framework (AuNCs@UiO-66) that may create new prospects for the development of novel sensing materials for biosensor applications. The resulting AuNCs@UiO-66 nanocomposite exhibits red fluorescence with a high quantum yield (11%), and the AuNCs are homogeneously distributed along UiO-66. Analytical and morphological characterizations of the resulting material were carried out by UV-visible spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy. The synthesized AuNCs@UiO-66 nanocomposite was used for the effective detection of Hg ions with a detection limit as low as 77 pM. Moreover, the fabricated sensors also successfully detected Hg in real water samples. This sensor is stable and highly fluorescent, developed using a simple fabrication method, and would be constructive for the detection of other metal ions and in biological applications.