We report a negative feedback loop based on proton-driven in situ formation of plasmonic MoO nanosheets. When the concentration of Cu is below a certain level, the reaction of Cu and glutathione (GSH) produces Cu and few protons. However, when the concentration of Cu is above a certain threshold, the reaction of GSH and Cu will generate enough protons in the system to initiate the redox reaction of GSH and MoO nanosheets, which generates plasmonic MoO nanosheets. This process in turn inhibits the reaction of GSH and Cu , which sequesters the excess Cu from the system. The formation of MoO nanosheets lowers the concentration of protons in solution and turns off the production of MoO nanosheets. More importantly, the threshold concentration of Cu can be easily regulated by changing the concentration of MoO nanosheets.