A quantitative life prediction method has been proposed to evaluate fatigue life during morphological evolution of precipitates in Ni-based superalloys. The method is essentially based on Eshelby’s equivalent inclusion theory and Mori-Tanaka’s mean field method. The shape stability and life prediction are discussed when the external stress and matrix plastic strain are applied. The calculated results show that the fatigue life is closely related with microstructures evolution of precipitates. The magnitude and sign of the external stress and matrix plastic strain have an important effect on fatigue life of Ni-based superalloys during the morphological evolution of precipitates.