Abstract It is well known that Hg(II) ion is one of the most toxic chemical species in the environment, thus developing new sensors for recyclable detection of Hg(II) with excellent sensitivity and selectivity is highly desirable. Herein, a new bipyridine-containing hydrazone-linked covalent organic framework (COF), termed Bpda-Bth COF, is synthesized using 2,2'-bipyridine-5,5'-dicarbaldehyde (Bpda) and benzene-1,3,5-tricarbohydrazide (Bth) as building blocks. Given that the obtained Bpda-Bth COF possesses good crystallinity, high chemical stability and rich functional N,N’-chelating sites from the bipyridine units, a novel COF-based quartz crystal microbalance (QCM) sensor, which can be prepared by the in-situ growth of Bpda-Bth COF on the amino-modified QCM chip, is developed for the determination of Hg(II) ion in aqueous solution. Remarkably, the resulting Bpda-Bth COF-based QCM sensor can monitor Hg(II) ion in real-time and online with excellent selectivity, relatively low detection limit (58 ​nM) and good recyclability (at least five cycles). Moreover, fluorescence spectroscopy, X-ray photoelectron spectroscopy and zeta potential measurements are further conducted, which indicate that the highly sensitive and selective detection of the COF-based QCM sensor toward Hg(II) is assignable to the specific coordination interaction between Hg(II) ion and the N,N’-chelating sites in the pore wall of the bipyridine-containing Bpda-Bth COF. To the best of our knowledge, this is the first report on the development of COF-based QCM sensor for detecting Hg(II) ion. Our work demonstrates that COFs with specific functional sites can be designed and used as ideal sensing materials to fabricate novel QCM sensors for the targeted detection of metal ions.