Abstract: Nuclear security is an important part of national security and the lifeline of the development of nuclear energy. In the event of an accident at a nuclear power plant, aerosol particles formed by the release of fission products from the reactor core fuel may be released into the surrounding environment through normal leakage of the containment vessel, thereby causing radioactive harm to the public. The main methods of aerosol removal in containment include natural deposition and spray removal. Therefore, exploring the natural deposition and spray removal characteristics of aerosols is of great significance for studying the removal rules of radioactive aerosol particles under accident conditions. In this study, the PISAA (program integrated for severe accident analysis) integrated severe accident analysis software developed by China Nuclear Power Engineering Co., Ltd. was utilized to undertake program simulation verifications of the AHMED experiment, the FABCS experiment, and the COSTTHES experiment respectively, with an aim to address the phenomena of single-particle-size aerosol moisture absorption growth, multi-zone collision coalescence, and spray removal. The results were subsequently compared and analyzed. The validation scope included the natural deposition of aerosols under multi-zone collision coalescence and aerosol spray removal. The experimental results show that the natural deposition of aerosols shows an exponential pattern as a whole. For the natural deposition of aerosols at different temperatures, the deposition velocity of aerosols increases with the temperature due to the thermophoresis. The spray of containment can significantly enhance the settlement of aerosol. The attenuation rate of aerosol is the fastest in the first five spray times, and then gradually slows down. Meanwhile, the removal coefficient of aerosol increases with the spray flow rate. The simulation results of the program show that the PISAA program can simulate and verify the natural deposition and spray removal behavior of aerosol accurately, and the simulation results are in good agreement with the experimental data. The number of zones has a certain influence on the multi-zone collision agglomeration of aerosols, which is mainly concentrated in the early stage of aerosol deposition. The more zones there are, the closer the simulation curve is to the experimental data. When the normalized aerosol concentration is above 20%, the maximum relative error of the total concentration simulation curve of the FABCS natural deposition experiment at normal temperature is only 4.83%, and the maximum relative error of the simulation curve at the spray experiment flow rate of 84 L/h is only 4.4%. This study helps to understand the behavior of aerosol natural deposition and spray removal in containment, and also provides support for further validation and improvement of the function of PISAA procedure.