Abstract: Objective With the continuous development of aerospace technology, it is very important to ensure that the space engine can still be competent for the subsequent spacecraft launch mission after the test run. The present study proposes a fatigue life prediction method based on X-ray diffraction to effectively assess reliability of space engine. Methods Optical microscope (OM), energy spectrum analysis (EDS), electron backscattered diffraction (EBSD) and in-situ fatigue X-ray residual stress measurement are used to investigate high frequency and low cycle fatigue damage behavior at room temperature, as well as the correlation between low cycle fatigue life and residual stress in different directions and regions of gas tungsten arc welding (GTAW) welded joints of nickel-based superalloy GH4169. Results The results demonstrate that fatigue fracture occurs in the heat-affected zone adjacent to fusion line under the plastic strain amplitude. As the fatigue life increases, both transverse and longitudinal residual stresses of welded joints decrease. It is found that longitudinal residual stress at the center of weld decreases most obviously with the increase of fatigue life of weldment. Conclusion A significant correlation is observed between longitudinal residual stress at the center of weld and fatigue life of weldment, with a pronounced “zero-direction trend” phenomenon. Fatigue fracture takes place when longitudinal residual stress reaches 0. The key considerations in the measurement process are summarized to provide guidance for precise prediction of fatigue life of weld in engineering applications.