210Po, a highly toxic element with strong volatility, is one of the main source terms of a Gen-IV lead-cooled fast reactor (LFR). Therefore, the radioactive safety caused by 210Po has become an important topic in LFR-related research. In order to simulate the behavior of 210Po in an LFR, this work developed a multi-physics model of an LFR from the perspective of radioactive transport. Considering the effects of nuclide decay, cover gas leakage, containment ventilation, and Po aerosol deposition, a comprehensive simulation was carried out to evaluate the sensitivity of those effects on the 210Po distribution in detail. Preliminary results indicate that during normal operation, most of the 210Po in the LBE exist in the form of PbPo, and around 10–9 of 210Po could evaporate from the LBE into the cover gas, and then further leak into the containment. In addition, even if the leakage rate of 210Po in the cover gas into the containment is maintained at 5‰ per day, due to the deposition of Po aerosol, the 210Po contamination on the inner surface of the containment is still below the radioactivity concentration limits.