Co-based coating was prepared by plasma cladding on FV520B substrates. Microstructure of the coatings was observed by scanning electron microscope. Finite element simulation as a predictive method to research the stress distributed after thermal cycling. Thermal fatigue resistance of the coating-substrate was evaluated at temperature of 600 °C, 700 °C, 800 °C, and 900 °C. Results indicate that the surface/interface structure has excellent thermal fatigue resistance at 600 °C, and the thermal fatigue crack initiated near the interface and extended along the grain boundary. The difference of expansion coefficient of the coating and substrate is small near 600 °C, and the difference increased when the temperature climbed above 600 °C. The diffuse elements could be found near the interface after the thermal cycle, and the dislocations and precipitated phase were observed.