The residual stress is one of the main factors to cause the failure of thermal barrier coatings. In this paper, a sinusoid curve with different amplitudes was used to model the roughness of interface between ceramic top coat (TBC) and bond coat (BC) in thermal barrier coatings and the effect of interface roughness on residual stress distribution was analyzed. Besides, the effect of roughness on interfacial crack nucleation and propagation under load was simulated with cohesive zone model. Results show that the interface roughness has a significant effect on residual stress distribution and crack nucleation and propagation. With the increase of interfacial roughness, the maximum tensile/compressive stress near the interface also increases in the TBC/BC. When applying a certain tensile displacement load, the maximum damage and crack firstly take place in the peak and valley of minimum amplitude.