The material cracking behavior in the reactor is generated under the irradiation effect accompanied by thermal expansion, fission product diffusion, and mechanical load. In this study, the energy release rate for crack growth under irradiation has been deduced synthetically according to the thermodynamically consistent method and numerically implemented by the finite element method (FEM). Variation in the total energy was obtained based on the principle of minimum potential energy in which the dissipative behavior can be characterized by fission energy, irreversible heat flow, and diffusion of fission products. Through calculating the variation in the total energy with respect to crack length, the energy release rate for crack propagation was analytically represented. Additionally, the total energy release rate for deflective cracks was also derived to predict the crack kinking. Furthermore, the numerical implementation of the presented model was performed by FEM and the equivalent domain integral method. Effects of irradiation on the physical fields and the energy release rate near the crack tip were investigated and analyzed in such a complex I-TDM coupling system. This study can be developed to investigate fracture problems, assess structural integrity, and evaluate material strength of irradiated materials.