A double-layer paddle piglet milk mixing tank was designed to study the effects of agitator parameters in piglet milk mixing tank on mixing effect of milk.The method combining CFD numerical simulation and response surface analysis was used. A four factor and three-level orthogonal simulation experiment was designed by taking the rotating speed, layer spacing, paddle angle and distance from the bottom as the design optimization parameters, and the mixing power, mixing time and average temperature rise rate as the response indexes. The regression model of response index was established. The parameters of double-layer paddle agitator were optimized. The results showed that the rotating speed and blade angle significantly affected the mixing power. The rotating speed, layer spacing, blade angle and distance from the bottom had a significant impact on the time of mixing. The rotating speed had an extremely significant impact on the average rise rate of temperature. The layer spacing and blade angle had a significant impact on the average rise rate of temperature. The rotating speed had the greatest impact on the performance of the agitator. The response surface regression model had good fitting. The parameters optimized by the response surface regression model were the speed of 80 r/min, the layer spacing of 170 mm, the blade angle of 30°, and the distance from the bottom of 100 mm. Compared with that before optimization, the stirring power and the time of mixing was reduced by 27.08% and 70.15%, respectively. The average rise rate of temperature was increased by 9.57%. The cloud diagram distribution of turbulent flow energy and temperature were significantly better than those of the primary model. It will provide theoretical basis and reference for the design and application of agitator in piglet milk preparation tank.