The relationship between internal stress and thermomechanical fatigue (TMF) in a Ni-based single-crystal superalloy is studied by neutron and X-ray diffraction. The extents of internal stress, deformation, lattice mismatch, and distortion during TMF are characterized by the determined deviatoric stress invariants and lattice parameters and compared with relevant microstructural information from scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results show that, in general, the macroscopic stress, plastic deformation, lattice mismatch, and distortion have all increased during TMF. The lattice mismatches of the TMF samples are at a high level, where the values along [100]/[010] are negative, but those along [001] are positive. The tetragonal lattice distortion of the c matrix is slightly greater than that of the c¢ precipitates, where the c/a values of the c matrix are smaller than 1, but that of the c¢ precipitate larger than 1. The c matrix yields and becomes hardened at the initial TMF cycle and gradually loses most of its strength during the earlier TMF cycles, associated with stress relaxation and homogenous deformation. However, the c¢ precipitates yield and become hardened later, bearing the most stress up to the necking of the superalloy. This process is associated with a buildup of stress and significant concentrated and inhomogeneous distribution of deformation in the c¢ precipitate. The residual deformation states of the superalloy and its component phases at the earlier TMF are basically shearing, and only become stretched at a later stage of TMF. The microstructure of the TMF samples shows an initial stage of rafting, where the dislocations are accumulated at the c=c 0 interfaces of the c matrix channels, but both dislocation networks and stacking faults are inhomogeneously distributed in the c¢ precipitates.