SiO2 microspheres were synthesized in a controlled manner via St?ber method by using a microreactor and a batch reactor in series to achieve rapid mixing of the reactant and flexible adjustment of the aging time. The phase and morphology of the as-prepared SiO2 were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscope (TEM). The results showed that the mean particle size and dispersity of the SiO2 microspheres depended on the competition between the tetraethyl orthosilicate (TEOS) hydrolysis reaction and the silanol monomer condensation reaction, and were also significantly influenced by the mixing rate of reactants in the initial period. The monomer addition model was employed to explain the experimental results. When the aging temperature increased from 25℃ to 75℃, the mean particle size of SiO2 microspheres decreased from 472 nm to 200 nm, with little change in dispersity. Because the reaction rates of TEOS hydrolysis and silanol monomer condensation increased with the increasing aging temperature, the supersaturation degree of silanol monomer immediately exceeded the critical supersaturation for homogeneous nucleation at higher aging temperatures. A large number of nuclei was formed, causing the formation of smaller microspheres. When the concentration of aqueous ammonia was increased from 0.8 mol/L to 5.6 mol/L, the mean particle size of SiO2 microspheres increased from 34 nm to 261 nm, and the dispersity became better. At higher ammonia concentration, more ethoxyl groups were hydrolyzed in a single TEOS molecule to produce silanol monomers with more silanol groups. This kind of silanol monomers could condense into siloxane networks at a faster rate, leading to larger particle sizes. When the water concentration increased to 35.6 mol/L or the TEOS concentration increased to 1.0 mol/L, multiple nucleation or continuous nucleation occurred in the solution, resulting in a dramatic deterioration of the dispersity of SiO2 microspheres. Increasing the Reynolds number (Re) or reducing the channel inner diameter led to the formation of monodisperse SiO2 microspheres, which could be attributed to the faster mixing between the reactants.