Zr-containing metal-organic frameworks (MOFs) exhibit a good performance of catalyzing the hydrolysis of chemical warfare agents, which is closely related to the size of MOF particles and its defects, but these two factors are often intertwined. In this article, we synthesized UiO-66-NH2 nanoparticles using a microwave-assisted hydrothermal method. By using a new modulator 4-Fluoro-3-Formyl-Benzoic Acid (FFBA) in different proportions, MOF particles with the same defect degree but different scales and those with similar sizes but different defect degrees can be obtained. The performance of the obtained MOF particles to catalyze the hydrolysis of the nerve agent simulant, dimethyl 4-nitrophenyl phosphate (DMNP), was investigated, and the effects of single factors of size or defect were compared for the first time. As the size of the obtained MOF particles increased from 81 nm to 159 nm, the catalytic degradation efficiency toward DMNP gradually decreased, and the half-life increased from 3.9 min to 11.1 min. For MOFs that have similar crystal sizes, the catalytic degradation half-life of MOF3 is only 5 min, which is much smaller than that of MOF5 due to the defects increase from 1.2 to 1.8 per Zr6 cluster.