Quantitative assessment of the initial damage state of a structure and fatigue life prediction on this basis, especially when it is sensitive to manufacturing quality, is crucial for both engineering application and material science. Traditional solutions based on fracture or damage mechanics either require precise constitutive relationships and cumbersome physical mechanism models or simply ignore the initial damage state. This study developed a novel equivalent initial flaw size (EIFS) quantitative evaluation method for film cooling holes in Nickel-based single crystal superalloy turbine blades to address the strong correlation between the initial damage in and fatigue life of the material. The temperature and stress field differences at the edges of holes with different inclination angles were simulated using a solid-liquid-gas three-phase level-set model and considered to represent the same initial damage. Next, the coupled damage–fracture mechanics model was used to achieve equivalent crack insertion, crack propagation, and fatigue life prediction based on the EIFS. The results indicate that this method can provide a highly robust EIFS distribution interval and that the crack geometry correction factor and EIFS distribution range are weakly correlated with the loading conditions (with an error within 2 %). The EIFS-based fatigue life predictions demonstrated a notable degree of accuracy, with the majority of the predicted and experimental fatigue lives falling within a three-fold dispersion band and all predictions remaining confined within a five-fold dispersion band of the actual lifetime. These results represent a substantial advancement in accuracy compared to traditional damage mechanics predictions. Therefore, this study provides a powerful approach for evaluating the fatigue life of turbine blades considering the initial damage state and can be widely applied to guide drilling process optimization and blade fatigue analysis.