In this work, the first chloride ion sensor based on QD-lucigenin nanoparticles is reported. The mechanism uses the ability of semiconductor QDs to engage in short range exchange processes, leading to fluorescence changes. An acridinium dication (lucigenin) which is an electron acceptor, was self-assembled on the surface of negative charged QDs (capped with mercaptopropionic acid). Mutual quenching of the lucigenin and QD were observed. From a sphere of action, Perrin-type model, exchange was estimated to occur over a range of the order of 2 nm. The possibility of spin-orbit coupling (SOC) or electron transfer between the QD and the lucigenin dication (Luc(2+)) is discussed. The radical cation Luc(+*) was not identified, but electron transfer from the QD conduction band to the Luc(2+), then electron transfer back, from the Luc(+*) to the QD valence band, could lead to mutual quenching, without build up of Luc(+*) . SOC between the QD and lucigenin, with or without charge transfer being involved, can also account for the results obtained. Lucigenin is also a chloride-sensitive indicator dye, with a sensing mechanism based on SOC. In the QD-MPA-lucigenin conjugate luminescence is restored by adding chloride ion. Thus, the presence of chloride is transduced into an enhancement of the luminescence of QDs. Using this operating principle, a chloride ion sensor based on CdSe-ZnS core-shell QD nanoparticles, showed a very good linearity in the range 1-250 mM, with a detection limit 0.29 mM and a RSD of 2.5% (n = 10). In a study of interferences, the chloride sensitive QDs showed good selectivity to most of the other anions tested. The versatility of the system was also demonstrated in terms of fluorescent emission wavelength, which could be selected across a wide range through choice of QDs. Examples are shown for lambda(max) = 500, 540 and 620 nm. The results from samples mimicking physiological conditions suggested very good applicability in the determination of chloride ion in physiological samples.