The flue gas desulfurization reactor by spray drying adsorption plays a crucial role in the process of gas purification. This study employed the multi-phase particle-in-cell method to accurately model the three-dimensional motion of particles of different sizes in the flue gas desulfurization reactor. The double-film theory was utilized to simulate the heat and mass transfer processes of desulfurization slurry droplets. Additionally, this study conducted a comprehensive analysis of various factors affecting gas-solid flow and mass transfer processes, including flue gas inlet velocity and temperature, Ca/S molar ratio, slurry particle size, and slurry temperature. The results demonstrate that the simulated and experimental results are in good agreement, validating the reliability of the developed model. The axial mass fluxes of gas and particles exhibit contrasting distributions in the central part and near the wall, with the turbulent viscosity being particularly pronounced in the top nozzle region. The inlet velocity of flue gas has a limited effect on the axial mass flux of particles, whereas the Ca/S molar ratio exerts a more significant influence. Furthermore, the Ca/S molar ratio has a substantial impact on the spatial distribution of flue gas temperature. The inlet velocity of flue gas and slurry particle size are negatively and positively correlated with particle residence time, respectively. Based on the mass transfer characteristics, the reactor interior can be divided into three zones: a high-efficiency desulfurization zone, a low-efficiency desulfurization zone, and a partial desulfurization zone. For the investigated operating conditions, the desulfurization efficiency is most strongly influenced by the slurry particle size, followed by the flue gas inlet velocity, Ca/S molar ratio, flue gas inlet temperature, and slurry temperature.