The invention relates to a strong interference resistance control method of a flexible spacecraft attitude control system, targeting a flexible spacecraft attitude control system having a nonlinear dynamic state, flexible vibration and measurement noise multi-source interference. The strong interference resistance control method of the flexible spacecraft attitude control system comprises steps of establishing a multi-source interference resistance model according to a nonlinear euler angle kinematics and posture dynamics of the flexible spacecraft to finish multi-source interference mathematic representation and modeling, designing an interference observer on the basis of mathematic representation and modeling to perform estimation on flexible vibration, designing an extended state observer to perform estimation on a system state and a non-linear dynamic state according to output of an interference observer, designing a strong interference resistance controller according to the interference observer and the extended state observer and solving an unknown gain on the basis of pole configuration to finish design of a strong interference resistance controller according to estimation values of the interference observer and the extended state observer. The strong interference resistance control method of the flexible spacecraft attitude control system is strong in interference resistance, high in control accuracy and can be applied to high accuracy control of the flexible spacecraft.