Abstract: As a new type of energy system, thermoelectric isotope battery system is widely used in deep space and deep sea exploration missions. Strontium titanate fuel is used as the heat source for thermoelectric isotope batteries. The radioactive isotopes of ⁹⁰Sr and ⁹⁰Y in the strontium titanate heat source emit β ray, which interact with substances to produce bremsstrahlung radiation. Due to the strong penetrating power of bremsstrahlung radiation, it is necessary to install a shielding layer on the surface of the isotope radioactive source strontium titanate to reduce the radiation dose of the thermoelectric isotope batteries. When the thickness of the shielding layer exceeds a certain value, the statistical error of the Monte Carlo method increases significantly. Variance reduction technique can be used to improve the accuracy of shielding calculation for thermoelectric isotope batteries. At the same time, the direct electron transport simulation takes a long time, which is much longer than the photon simulation, and the photons produced by the electrons can be processed by the thick target bremsstrahlung (TTB) model, thus improving the computational efficiency. In this paper, the variance reduction technology of cosRMC program and the application of TTB radiation model in the shielding calculation of isotope batteries were studied and verified. Based on the design scheme of SNAP-21 structure in the United States, the thermoelectric isotope battery is modeled by cosRMC program. The influence of depleted uranium on the surface dose rate was analyzed by changing the thickness of the radial and axial outer shielding layers of the thermoelectric isotope battery, and the calculated results were compared with those of MCNP program. The comparison of the two programs shows that the statistical error of dose rate of depleted uranium shield surface calculated by cosRMC and MCNP is in good agreement with ±3σ range when different thickness shielding layers were used in radial and axial directions of thermoelectric isotope batteries. In order to reduce the statistical error of the calculated results, the cell importance variance reduction was used. The results show that the statistical error of the cosRMC and MCNP programs decreases at the radial 5 cm and axial 4 cm of the battery by 52.515% and 39.338%, respectively. The dose rate relative errors calculated by cosRMC and MCNP are in good agreement within the range of ±3σ, which further verifies the accuracy of cosRMC program in the calculation of thermoelectric isotope battery shielding.