In order to research influences of hydrodynamic effect on asphalt mixture anti-fatigue performance under different material composition, laboratory equipment is developed for simulating the asphalt pavement affected by water, load and temperature. Seven types of asphalt mixture are generated with void ratio of 6%, 10% and 14%, gradation of AC-16, SMA-16 and SAC -16 and asphalt of A-90, A-110 and A-130; stress-fatigue equation parameters change of these mixture after hydrodynamic effect are analyzed by comparison. The results have shown that anti-fatigue performance of the asphalt mixture is reduced after hydrodynamic effect. Under fatigue load, asphalt membrane of mixture after hydrodynamic effect is easier to spalling. 10% is unfavorable void ratio of AC concrete, it can cause fatigue life reduction and stress sensitivity increase. When the void ratio is 10%, suspension structure of the asphalt concrete follows the larger influence of hydrodynamic effect on anti-fatigue performance than the skeleton structure and high penetration asphalt concrete is larger than low penetration in the influence.