The hysteresis loops, stress and strain behavior, lifetime behavior and fracture characteristic of 4Cr5MoSiV1 hot work die steel at a wide range of mechanical strain amplitudes (from 0.5% to 1.3%) during the in‐phase (IP) and out‐of‐phase (OP) thermomechanical fatigue (TMF) tests cycling from 400 °C to 700 °C under full reverse strain‐controlled condition were investigated. Stress‐mechanical strain hysteresis loops of 4Cr5MoSiV1 steel are asymmetric, and stress reduction appears at high‐temperature half cycles owing to a decrease in strength with increasing temperature. 4Cr5MoSiV1 steel always exhibits continuous cyclic softening for both types of TMF tests, and the cyclic softening rate is larger in OP loading condition. OP TMF life of 4Cr5MoSiV1 steel is approximately 60% of IP TMF life at the same mechanical strain amplitude and maximum temperature. Lifetime determined and predicted in both types of TMF tests is adequately described by the Ostergren model. Fracture surfaces under IP TMF loading display the striation and tear ridge, showing quasi‐cleavage characteristics, and the cracks are less but longer. However, fracture surfaces under OP TMF loading mainly display the striation and dimple characteristics, and the cracks are more and shorter.