In subsea HPHT wells, annular pressure buildup caused by thermal expansion of fluid endangers well integrity. The conventional well design is not secure for subsea HPHT wells. It is significant to assess the risk from annular pressure buildup and provide solutions. Considering the interactions and pressure changes of different annuli, the calculation model of annular pressure buildup in multiple casing annuli is established. This model expands the scope of application of existing models. In view of temperature-dependent coefficient of thermal expansion and compressibility, the calculation method based on temperature increment is adopted to improve the calculation precision of annular pressure buildup. Research results show that the annular pressure buildups are various under the condition of different temperature ranges and same temperature change, and the annular pressure buildup in high temperature range is greater than that in low temperature range. The casing load arising from annular pressure buildup reaches or even exceeds the casing load according to conventional design. The research methodology is applied to a subsea HPHT well. The potential risk is discovered in the conventional casing design when annular pressure buildup occurs, and the casings are optimized design to deal with the issue. Furthermore, the mitigation measures for annular pressure buildup are recommended to ensure the well integrity of subsea HPHT wells. The research in this paper provides the reasonable calculation approach and mitigation measures of annular pressure buildup.