The effect of S impurity on adhesion of Fe(110)/Al2O3(0001) interface is studied by the first-principles plane wave pseudopotential method within the density functional theory. It is shown that S impurity prefers to occupy the site of Fe3 at Fe(110)/Al2O3(0001) interface substitutionally due to the smallest interface segregation energy. The adhesion of Fe(110)/Al2O3(0001) interface is mainly governed by the interaction between Fe and O atoms on both sides of interface. The calculation results of the partial density of states, Mulliken overlap population and the electron density all suggest that Fe-O interaction is weakened by the segregated S impurity at Fe/Al2O3 interface, and the presence of S impurity gives rise to stronger electrostatic repulsion between Fe and O atoms across Fe/Al2O3 interface, which all leads to a reduced adhesion for Fe/Al2O3 interface. As a result, the results obtained by the first principles can give us a deeper understanding of the mechanism of a reduced interface adhesion and the oxidation film spallation by the segregation of S impurity at FeCrAl alloy interface.