In order to solve the problem of coupling heat transfer between supercritical carbon dioxide (S-CO2) and liquid lead bismuth alloy in printed circuit board heat exchanger (PCHE) under a certain working condition, a PCHE heat transfer unit is established, which simplifies the plate into a single hot runner and two cold runner, and draws a three-dimensional model. At the same time, due to the special physical properties and heat transfer mechanism of liquid lead–bismuth alloy, it is very different from conventional fluid, and cannot be substituted into the model by the same Prandtl number calculation method as S-CO2. Based on the chang-tak model, UDF is developed to calculate Prandtl number of lead–bismuth alloy, and the coupling heat transfer characteristics of S-CO2 and liquid lead–bismuth alloy are studied by numerical simulation. The results show that the heat transfer coefficient of the hot side and the cold side decreases rapidly in a short distance after the entrance, and then becomes stable. The heat transfer coefficient of the cold side is not affected by the flow rate of the hot side. Due to the influence of the cold side inlet effect, the heat transfer coefficient at the hot side outlet will increase sharply when the flow rate is small. When only the cold side flow changes, the heat transfer coefficient increases gradually with the increase of the cold side flow. The CO2 flow acceleration effect increases the turbulence intensity, intensifies the fluid turbulence, enhances the disturbance to the boundary layer, and thus increases the convective heat transfer coefficient. Due to the influence of inlet effect and flow boundary layer, the heat transfer coefficient of the cold side inlet will decrease rapidly from a large value. Because of the inlet effect of the cold side inlet, the heat transfer coefficient at the hot side outlet will also increase sharply. As the Reynolds number of the cold side inlet increases gradually, the convective heat transfer intensity increases greatly. The overall heat transfer coefficient and Nu number of the cold side channel and the hot side channel show opposite trend, which may be because the increase of heat transfer reduces the temperature of LBE faster, and the density is negatively correlated with temperature. The increase of density leads to the slowdown of flow and the thickening of boundary layer.