Abstract: Ferritic/martensitic (F/M) steels are regarded as the ideal candidates for structural materials in advanced nuclear reactors because of their high thermal conductivity, low thermal expansion and high resistance to irradiation. However, in contact with oxygenated coolants (air, water and liquid metals), they undergo oxidative corrosion and multiple layers of oxides are formed on their surface. In addition, F/M steels must be subjected to high doses of neutron irradiation in the reactors in service. The irradiation not only leads to increased temperature and thermal stress, but also induces defects, which increases the diffusion rate of Fe atoms outward and O atoms inward, further accelerates the growth rate of the oxide layer. The growing oxides not only reduce the thermal conductivity of the structural material, but also detach from its substrate under stress, leading to a thin substrate and a reduction in the mechanical properties of the material. Therefore, the effect of irradiation on the stability of the oxide layer must be clarified for the safe operation of the reactor. In this paper, the interface stability of a bcc-Fe and FeCr₂O₄ with or without a vacancy was investigated using a first principles calculation method. Firstly, the Fe(001) surface and FeCr₂O₄(001) surface with Fe- and CrO-termination (Fe^T and CrO^T) were constructed and optimized by their surface energies and inter layer distances. The surface energy of FeCr₂O₄(001) with CrO^T is lower than that with Fe^T in oxygen-rich and iron-rich environments, which is thermodynamically more stable. Based on the optimized Fe(001) with three symmetry sites (bridge, hollow and top) and FeCr₂O₄(001) surfaces with Fe^T and CrO^T, constructed six different configurations of Fe(001)/FeCr₂O₄(001) interfaces and evaluated the interface stability by interface energy and adhesion work. The results show that the CrO^T-hollow model with the lowest interface energy and the largest adhesion work is the most stable model. Based on the most stable model, the most stable position of a vacancy was investigated by calculating the vacancy formation energy at the interface and nearby. The results show that Fe vacancies are more likely to be formed and distributed in the first layer on the Fe side of the bcc-Fe/FeCr₂O₄ interface, which is consistent with the experimentally observed vacancies in the internal oxidation region. By comparing the adhesion work of the interface with and without the most stable vacancy, it shows that the minimum adhesion work of the interface with vacancies decreases and the fracture surface changes from the bcc-Fe/FeCr₂O₄ interface to the second layer on the FeCr₂O₄ side. This suggests that irradiation-induced defects not only make the oxide layer more susceptible to detachment, but also change the fracture behavior of the oxide layer.