Abstract: A large number of dissimilar metal welded materials exist in nuclear power structures, so the accurate evaluation of crack propagation in welded region is highly relevant to the safe service of nuclear power equipment. Due to the significant nonhomogeneity of the materials in the welded region, the traditional J-growth path integral theory is no longer applicable to welded material. Meanwhile, a large amount of feedback from operating experience shows that the crack propagation in the welded region presents an obvious deflection phenomenon. Combined with the extended finite element method, this research established an effective technology to simulate crack propagation in the welded region of dissimilar metals based on the interaction integral theory. By using domain-independent interaction integral, it could accurately calculate the stress intensity factors of an arbitrary crack in the welded region. The prediction of crack propagation path could be realized after using crack propagation criteria such as maximum circumferential stress. By comparing the calculation results of proposed method with the analytical solutions given in the reference, the tiny relative error (<1.5%) indicates the accuracy and effectiveness of the current method. The welded regions in real nuclear power equipment were taken as the research object, and several different regions were selected for compact tensile fatigue tests. The comparison between the experimental results and the simulation results shows that the current method can effectively predict the crack propagation path (the relative error is less than 20%). The study finds that due to the material properties presenting obvious nonhomogeneous characteristics in the welded region, the stress at the crack tip is constantly changing during the crack propagation process. When the crack grows, according to the maximum circumferential stress criterion to determine the direction of its expansion. It can be found that the crack will be deflected at a certain angle, and it is not an Ⅰ-type crack expansion. This reflects the complexity of fracture behavior for nonhomogeneous material in the welded region, and the crack propagation path strongly depends on the distribution state of material properties near the crack. In summary, the numerical method based on the domain-independent interaction integral given in this paper is of practical engineering significance for the calculation of the stress intensity factors and crack propagation path prediction in welded regions.