By adding a spray chamber in front of the cyclone separator, spray agglomeration and heterogeneous vapor condensation were combined to improve the removal effect of the cyclone separator on fine particles, which is used for the deep treatment of high-humidity industrial flue gas and fine particles. Fine particles can form agglomerates through the capture effect of micron droplets, and can also grow in size through heterogeneous vapor condensation in supersaturated water vapor environment, thus being effectively removed by cyclone separators. Supersaturated water vapor environment was a necessary condition for heterogeneous vapor condensation. Numerical simulation results showed that supersaturated water vapor environment can be formed in the spray chamber when the relative humidity of the original flue gas was high, and the higher the relative humidity, the higher the supersaturation and the larger the supersaturation area. The experimental results indicated that spray agglomeration and spray coupling heterogeneous condensation increased the particle removal efficiency of the cyclone separator by 11.6 % and 22.6 %, and the removal efficiency in the 2–4 μm “fish-hook” range was increased by 21.6 % and 41.7 %, respectively. This technology was successfully applied for the first time in the deep treatment of the tail gas in Fluid Catalytic Cracking (FCC) catalyst production industry, which can ensure that the particle emission concentration was within 20 mg/Nm3.