A novel and versatile method for one-pot and in situ generation of bioreducible and acid labile nanogels/microgels simply via adding water into the polymerization system is reported. The produced polymers inthe polymerization system become temperature-sensitive and less soluble after adding water, and hencethey collapse together, forming nanoparticles. Subsequently, the disulfides inside the nanoparticleundergo intermolecular disulfide exchange to crosslink the nanoparticle into a bioreducible and acidlabile nanogel/microgel. The size of the nanogel/microgel can be easily controlled by thepolymerization time and the amount of water added. The formed nanogel/microgel is redox and pHresponsive, and biocompatible.