In this paper, a mechanism of anti-oxidation coating design based on the inhibition effect of the interface layer on the diffusion of ions within oxide scale was introduced. The Fe2+ ions diffusion behavior in Fe3O4, Cr2FeO4, and FeAl2O4 were studied by molecular dynamics method of Nudged elastic bond. As the result shown, Fe2+ ions tended to diffuse through the vacancy at tetrahedral site in Cr2FeO4 and FeAl2O4, but diffuse through the octahedral vacancy in Fe3O4. When temperature ranged from 1073 to 1325 K, the energy barrier of Fe2+ ions diffusion in Cr2FeO4 was higher than that of FeAl2O4, and both of that were still obvious higher than that in Fe3O4. A new anti-oxidation coating was prepared based on the inhibition of interface layer consisted of FeAl2O4 to protect the carbon steel S235JR at 1200 degrees C for 2 h. The FeAl2O4 region was formed and observed at the interface between coating and Fe element diffusion area, and the mullite phase was distributed outside of the FeAl2O4 region. Comparing to the bare sample, the prepared coating exhibited an excellent anti-oxidation effect.