Abstract: The offshore nuclear power plant site adopts a secondary circulation cooling water supply method, equipped with large countercurrent seawater natural ventilation cooling towers. Due to the effect of cooling towers as tall buildings and the mist plume emitted from cooling towers on the diffusion of airborne radioactive substances, it is necessary to conduct research on the effect of large natural ventilation cooling towers on the diffusion of nuclear power plant sites based on the engineering layout. The effects of cooling towers and their plumes on the diffusion of airborne radioactive substances through wind tunnel experiments and numerical simulations were summarized in this study. According to the characteristics of wind distribution on representative nuclear power plant sites, in combination with the distribution of residential areas, the dominant wind direction E, the secondary dominant wind direction N, and the wind direction W from the cooling tower to the nuclear island were used as the experimental wind directions. The influence of cooling tower air inlet during the experiment was considered. The site is comprehensively affected by buildings and mountains, and the effect of buildings such as cooling towers on the site is dominant. No matter whether the thermal plume is discharged or not, the large natural ventilation cooling tower has entrainment effect, and the airborne pollutants discharged from the stack will enter the cooling tower through the air inlet at the bottom of the cooling tower and act as an elevated source for secondary discharge. The entrainment effect with hot plume discharge is more significant than that without hot plume discharge, and the concentration of pollutants discharged through the cooling tower significantly increases. The wind tunnel experiment results show that when the chimney is discharged at a height of 75 meters, the entrainment fraction of the large natural ventilation cooling tower is 29.8% when it is working, and 1.2% when it is not working. The numerical simulation results show that when the chimney is discharged at a height of 75 meters, the entrainment fraction of the large natural ventilation cooling tower is 25.28% when it is working, and 0.75% when it is not working.