Recently, luminescent metal−organic framework (MOF) materials have attracted considerable attention in fluorescence sensing. In this essay, we prepared a new clusterbased Ca II -MOFs {[Ca 1.5 (μ 8 -HL 1 )(DMF) 2 ]•DMF} n (1) with good water dispersibility, excellent photoluminescence properties (FL quantum yield of 20.37%) and great fluorescence stability. Further, it was employed to design as an "off−on" fluorescence sensor for sensitive detection of L-cysteine. This proposed strategy was that fluorescence of Ca II -MOFs 1 was quenched for providing a low fluorescence background by the introduction of Pb 2+ forming the Ca II -MOFs 1/Pb 2+ hybrid system. The quenching effect could be ascribed to the static quenching mechanism because of the formation of ground-state complexes and coordination interactions between the free carboxyl of H 4 L 1 ligands of Ca II -MOFs 1 and Pb 2+ . Then, with the addition of L-cysteine into the Ca II -MOFs 1/Pb 2+ hybrid system, the fluorescence signal was immediately restored. This result was because the Pb 2+ was gradually released from the hybrid system by chelation interactions between the −SH groups of L-cysteine and Pb 2+ . This method received a relative wide linear range varying from 0.05 to 40 μM and a low detection limit of 15 nM for detection of L-cysteine. This proposed strategy was also successfully applied to detect L-cysteine in human serum samples with satisfactory recoveries from 95.9 to 101.5%.