Semi-batch operated reaction processes are necessary for some competitive reaction systems to achieve a desirable process selectivity and productivity of fine chemical products. Herein the structural and operating parameters of the teethed high shear mixers were adjusted to study the micromixing performance in the semi-batch operated system, using the Villermaux/Dushman reaction system. The results indicate that the rising of the rotor speed and the number of rotor teeth, the decrease of the width of the shear gap and the radial distance between the feed position and the inner wall of stator can enhance the micromixing level and lead to the decrease of the segregation index. Additionally, computational fluid dynamics calculations were carried out to disclose the evolution of the flow pattern and turbulent energy dissipation rate of the semi-batch operated high shear mixer. Furthermore, the correlation was established with a mean relative error of 8.05% and R² of 0.955 to fit the segregation index and the parameters studied in this work, which can provide valuable guidance on the design and optimization of the semi-batch operated high shear mixers in practical applications.