Abstract: The thermo-mechanical fatigue test of SDYZ hot-working die steel was carried out under the same temperature cycle and different strain amplitudes (0.7%-1.1%) by the strain control mode of tension-compression symmetry. The stress-strain hysteresis loop, cyclic stress response curve and microstructure change under different strain amplitudes were studied. The results show that the larger the strain amplitude, the larger the area surrounded by the thermo-mechanical fatigue stress-strain hysteresis loop of the test steel, the more serious the damage and the shorter the fatigue life of the test steel. The thermo-mechanical fatigue cyclic softening process could be divided into three stages of initial instability, continuous softening and failure. After the thermo-mechanical fatigue test, the martensite and carbides in the microstructure of the test steel were coarsened, and the coarsening degree of martensite and carbides decreased with increasing strain amplitude. With the increase of strain amplitude, the length and width of fatigue cracks increased.