This paper studies the frequency reliability of the main shaft system of Francis turbine-generator units based on nonlinear vibration. Taking the generator and turbine as an integrated system, the nonlinear coupling dynamic equations of the system are established by the finite element method. According to the dynamic equations, the frequent factors of system are obtained by the method of multiple scales. The criterion is used that the difference between the natural frequencies and driving frequencies including the frequent factors should be less than specific values. The reliability mode and the safety probability of the main shaft system of Francis turbine-generator units are defined as a series mode, and the frequency reliability analysis method for avoiding the resonance is proposed. Finally, an example is presented.