The adjustment of cellular redox homeostasis is essential in when responding to environmental perturbations, and the mechanism by which cells distinguish between normal and oxidized states through sensors is also important. In this study, we found thatacyl-protein thioesterase 1(APT1) is a redox sensor. Under normal physiological conditions, APT1 exists as a monomer throughS-glutathionylation at C20, C22 and C37, which inhibits its enzymatic activity. Under oxidative conditions, APT1 senses the oxidative signal and is tetramerized, which makes it functional. Tetrameric APT1 depalmitoylates S-acetylated NAC (NACsa), and NACsa relocates to the nucleus, increases the cellular glutathione/oxidized glutathione (GSH/GSSG) ratio through the upregulation ofglyoxalase Iexpression, and resists oxidative stress. When oxidative stress is alleviated, APT1 is found in monomeric form. Here, we describe a mechanism through which APT1 mediates a fine-tuned and balanced intracellular redox system in plant defence responses to biotic and abiotic stresses and provide insights into the design of stress-resistant crops.