As a renewable environmental-friendly liquid dielectric, natural ester has been widely used in oil-immersed power transformers due to its anti-aging and high ignition point properties. However, a large amount of unsaturated fatty acid exists in natural ester increases the chemical activity and deteriorates the oxidation stability. Currently, the initial oxidation temperature of the natural ester can be increased by adding the composite antioxidant. Therefore, the microscopic molecular simulation of the process of polysilsesquioxane (POSS) modified natural ester oxidation were studied in this paper. Natural esters and POSS additive models were established and simulated via molecular dynamics (MD) simulations based on ReaxFF (Reactive Force-Field). The results showed that the increase of temperature and heating time will promote the oxidation of natural ester, while POSS can effectively prevent this process. This article reveals the mechanism that POSS postpone the oxidation of natural ester and provides a certain guidance for the related experiments and theoretical studies of subsequent antioxidants