Accurate prediction of fatigue crack growth life of gas turbine blades under out-of-phase thermo-mechanical fatigue loading is of significance for safeguarding its structural integrity. In this study, a finite element analysis framework, integrating ANSYS and FRANC3D for joint simulation, is proposed to tackle the issue of residual stress-driven crack propagation in the “hot spot” of the turbine blade. Initially, a sequential thermal-structural coupling analysis of crack-free blade is conducted in ANSYS to accurately quantifies residual stresses induced by creep relaxation during thermal cycling. Subsequently, semi-elliptical initial cracks with specific width-to-depth ratios are introduced in the regions of large residual stresses, and the crack propagation process is numerically simulated based on linear elastic fracture mechanics and the Paris model using FRANC3D. It is discovered that the width-to-depth ratio of initial crack significantly influences the fatigue crack growth prediction life, 23.86% reduction in lifetime at compared to . Moreover, a critical crack depth of approximately 12 mm is obtained when rapid unstable fracture occurs. The research provides a vital theoretical foundation and technical support for the fatigue life prediction and structural optimization of gas turbine blades, thereby contributing to the enhancement of the safety and reliability of gas turbine operations.