As a vulnerable part of diesel engine, cylinder head is periodically subjected to the thermo-mechanical coupling loads. While due to the restriction of complex structures and working conditions, it makes the damage mechanism of thermo-mechanical coupling still unclear. In this research, thermo-mechanical responses are predicted successfully by load spectrums and the Sehitoglu theory. Then the effects of working loads on classified damage characteristics are analyzed with the equivalent cylinder head model. The results show that the deviations of temperature and stress are, respectively, within 10°C and 30 MPa, and it verifies the effectiveness of simulated component. Operating speed takes the greatest effect on the thermo-mechanical characteristics, and bolt force and gas pressure are negatively correlated with the responses of stress and strain. Fatigue life and damage are determined by the values of working loads. The effect of temperature load is the most dominant, MechDam and OxidDam increase substantially when operating speed exceeds 3500 r/min. The research will provide a theoretical reference for engineering design and optimization of cylinder head.