In order to solve the problem of high impurity rate and loss rate for the cleaning device in 4LZ-4.0 combine harvester of soybean, a three-factor and three-level response surface test was designed with the selected influence factors of screen angle(17.1°, 27.1° and 37.1°), fan speed(969, 1090 and 1212 r/min) and feeding speed(2.0, 2.5 and 3.0 kg/s), to test the loss rate and the impurity rate of the cleaning device and screen the optimal combination of cleaning parameters. The experimental results showed that the optimal combination of cleaning parameters obtained is: the sieve plate angle of 26.8°, the fan speed of 1075 r/min, and the feeding volume 2.3 kg/s, with the loss rate of 0.18% and the impurity rate of 2.07%, which are reduced by 0.26% and 0.44% compared with that before optimization. When the cleaning device of the harvester has the best performance, the mass ratio of soybean post-threshed mixtures decreases from 29.88% to 6.34% along the longitudinal direction of the cleaning screen, and decreases from 27.51% to 7.88%, and then increases to 18.96% along the horizontal direction of the cleaning screen, which shows an approximate “Y” shaped distribution of “more in front and less in back, more on both sides and less in the middle”. It can provide reference for the structure improvement of the cleaning screen.