Abstract: The performance of automotive water pump bearing seal is closely related with the magnitude of interference of the sealing lip. In this paper, mechanics of material and Hertz contact theory were applied to develop the model for calculating the contact stress distribution on seal and shaft surfaces, and used this model to analyze the relationship between the contact stress distribution and sealing lip’s interference. Micro-surface morphology of the shaft was simulated by taking advantage of the adaptive correlation function, moreover the alternating stress of sealing lip led by the surface micro-asperities were calculated within one revolution of the rotating shaft. The fatigue life prediction method of the seal was constructed according to rain-flow counting method and fatigue life calculation method, meanwhile the fatigue lives of the seal with different lip interferences were calculated. The present study can provide theoretical support for further research and application of the sealing technology of automotive water pump bearing.