Abstract. The fatigue damage behavior was experimentally investigated in different axial-torsional thermo-mechanical loading conditions for Ni-based superalloy GH4169. The strain controlled tests were carried out with the same von Mises equivalent mechanical strain amplitude of 0.8% in the temperature range from 360°C to 650°C. The results show that the fatigue life is drastically reduced when the axial mechanical strain and the temperature are in-phase, which can be due to that the creep damage is induced by the tensile stress at high temperature. Moreover, the fatigue life is further decreased when the axial mechanical strain and the shear strain are out-of-phase, which can be attributed to that the non-proportional hardening can increase the creep and the oxidation damages. Furthermore, the tensile stress is crucial to the nucleation of creep cavities at high temperature compared with the shear stress. The tensile and shear stresses all can increase the creep damage under fatigue loading at high temperature. In addition, the oxidation damage can be induced during cyclic loading at high temperature, and it can be increased by the tensile mean stress caused in non-isothermal loading.