Abstract: In order to study the effect of heat loss of the heat source on the output performance in small radioisotope thermoelectric generator, the output performance and thermal efficiency of the generators under different thermal insulation designs were thoroughly investigated. Finite element simulation software analysis is the most commonly used method by researchers, which can comprehensively consider the influence of multiple factors and is more convenient and accurate. Through COMSOL finite element simulation software, a cell of 46800 model size with a heat source power of 0.5 W was constructed, and the output power, conversion efficiency and effective thermal power of the radioisotope thermoelectric generator under vacuum were investigated. In order to reduce the radiation heat transfer between the internal surfaces of the generator, a measure of adding several thermal radiation shields between the heat source and the shell was adopted, while increasing the surface thermal resistance and the spatial thermal resistance. Therefore, the simulation research on the number of thermal radiation shields, the surface emissivity of the shields and the heat source, and the shielding layer gap were carried out. The results show that the thermal radiation shields as an insulating structure can achieve a larger temperature difference between the two ends of the thermoelectric transducer device and obtain a higher output power compared with SiO₂ aerogel. When the number of the thermal radiation shields is increased from 0 to 3 layers, the thermal efficiency is improved by 12.23%, and the maximum output power is increased by 4.09 mW, this mainly increases the thermal resistance of the space to reduce the radiative heat loss, the more shields there are, the less radiative heat loss there will be. When the surface emissivity is reduced from 0.20 to 0.05, the thermal efficiency and the maximum output power increased to 90.78% and 11.02 mW respectively, this mainly increases the surface thermal resistance to reduce the heat loss by radiation. The smaller the surface emissivity is, the less radiant heat lost will be. When the shielding layer gap is reduced from 1.50 mm to 0.30 mm, the reduction in shielding layer gap is equivalent to an increase in angle coefficient and a decrease in gap radiation heat dissipation. At this time, the thermal efficiency and maximum output power are only increased by less than 1% and 1 mW, respectively. Reducing the distance between the heat shields can be used as an auxiliary measure for heat insulation design. According to the simulation results, the number of shielding layers and the surface emissivity are the key considerations in the insulation design.