This study was designed to explore the synergistic enhancement of the spraying pretreatment section and axial flow cyclone on the separation of particles from gases. First, in the spraying pretreatment section, the effects of the gas flow rate, droplet flow rate, droplet diameter, and gas or droplet temperature on the collection efficiency of the particles and the supersaturation degree were analyzed. Then, the nucleation and growth process of fine insoluble particles were discussed. At last, combined with an axial flow cyclone, the influences of operating parameters on the separation efficiency and energy consumption were presented. Our results show that the spraying pretreatment can capture 80% of particles larger than 5 μm and can maintain a supersaturated environment. Fine particles (PM1.0) will be aggregated to above 6 μm quickly and removed in the axial flow cyclone with a separation efficiency of above 98%. In addition, the energy consumption of the integrated purification process in this study is reduced by 20.65%, on average, compared to that of an electrostatic precipitator. These findings provide new insights into the separation of fine particles in industrial applications.