Mercury ion (Hg2+), a bioaccumulating and toxic heavy metal, can cause severe damages to the environment and human health. Therefore, development of high-performance Hg2+ sensors is highly desirable. Herein, we construct a uniform dodecahedral shaped N-doped carbon decorated by single Fe site enzyme (Fe-N-C SAE), which exhibits good performance for Hg2+ detection. The N atom on Fe-N-C SAE can specifically recognize Hg2+ through chelation between Hg2+ and N atom, while the catalytic site on the single-atom enzyme acts as a signal amplifier. The Fe-N-C SAE-functionalized solution-gated graphene transistor exhibits a dramatic improvement in the selectivity and sensitivity of the devices. The sensor can rapidly detect Hg2+ down to 1 nM within 2 s. Besides, a relatively good repeatability and reproducibility for the detection of Hg2+ have also been found in our sensor platform. Our findings expand the application of single-atom catalysts in the field of food safety and environmental monitoring.