N,N'-dimethacryloylcystine dimethyl ester was used as cross-linker, and a series of redox-responsive PMAA (Polymethacrylic acid) nano-hydrogels were prepared by distillation-precipitation polymerization method. The composition, size distribution and morphology of the nano-hydrogels were characterized by fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and scanning electron microscope (SEM) respectively. The influences of the amount of cross linker, monomer and initiator, and the reaction time on the size and yield of the nano-hydrogels were investigated. The results demonstrated that various sizes of nano-hydrogels could be obtained by adjusting experimental conditions. Especially, the size of nano-hydrogels was significantly affected by the factors of amount of crosslinker and reaction time. Furthermore, optimum technological conditions were obtained by orthogonal experiment, in which the mole ratio of initiator, monomer and cross-linker was 1.1: 96: 2.9; the reaction time was 15 min. In addition, the PMAA nano-hydrogel showed good redox-responsive property. Under 10 mmol/L DTT condition, the PMAA nano-hydrogel could be degraded within 20 min.