Inorganic mercury (Hg2+) pollution of water reserves, especially drinking water, is an important issue in the environmental and public health field. Mercury is reported to be one of the most dangerous elements in nature since its accumulation and ingestion can lead to a series of permanent human diseases, affecting the kidneys and central nervous system. All the conventional approaches for assaying Hg2+ have some limitations in terms of bulky instruments and the cost and time required for the analysis. Here, we describe a miniaturizable and high-throughput bioluminescence sensor for Hg2+ detection in water, which combines the specificity of a living bacterial Hg2+ reporter cell, used as sensing element, with the performance of a silicon photomultiplier, used as optical detector. The proposed system paves the basis for portable analysis and low reactants consumption. The aim of the work is to propose a sensing strategy for total inorganic mercury evaluation in water. The proposed system can lay the basis for further studies and validations in order to develop rapid and portable technology that can be used in situ providing remote monitoring.