The friction behavior of cylinder seal greatly affects the dynamic position accuracy of the cylinder execution terminal under hydrothermal aging. So, the hydrothermal aging test, friction test, tensile and compression test, topography analysis and infrared spectroscopy analysis, and multiscale simulation were carried out for studying the effect of the hydrothermal aging on the friction performance of cylinder seal. It was found that when the aging temperature increases from 40 to 80°C, the dynamic friction forces of the cylinder seals increase by more than 15%; the friction force increases with the increasement of the initial mechanical stress. Aging makes rubber to be brittle and more cavities on the fracture surface and reduces the fractured activation energy of the nitrile rubber molecular chain.