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Fatigue failure is defined as the progressive degradation of the strength of a structural component during the manufacturing of machine tools. As the increasing demands for high product quality result in a continuing need to achieve improvements in fatigue reliability on machining tools, many researches have been focused on it in recent decades with a result of many valuable contributions. However, current researches always focus on the fatigue analysis of rigid components, and the dimension change, necessary design, and optimization are lacked, while the component of a product is always a rigid-flexible coupling multi-body system, which could affect the accuracy and reliability of fatigue analysis, and parameterization help designers see each dimension change. This paper proposed a process of component fatigue analysis based on rigid-flexible coupling virtual prototyping. In this paper, a crankshaft in the cold heading machine is taken as an example to show the rigid-flexible coupling fatigue analysis process in detail. After the parameterization of the crankshaft is proposed, the static analysis and optimization of the crankshaft is carried out. The dynamics analysis for rigidflexible coupling of the cold heading components is also proposed. The fatigue analysis for the crankshaft is discussed in detail. The crankshaft in the cold heading machine is given as an example, which demonstrates that the methodology is obviously helpful to fatigue analysis and simulation. The physical prototyping is also carried out to demonstrate the fatigue reliability. The crankshaft of cold heading machine is given as an example, which demonstrates that the methodology is obviously helpful to fatigue analysis and simulation.