There were some problems during peanut picking and harvesting, such as high loss rate and high impurity rate, which affected the harvest quality and increased the harvest cost. In view of the problems of high loss rate and high impurity content in process of axial peanut harvester, according to the physical characteristics and air flow characteristics of various types of particles in peanut pod mixture, a winnowing system was designed. The motion state of four kinds of particles in air separation space were simulated and analyzed by Fluent-EDEM coupling analysis. Through numerical simulation experiments under different conditions, the working parameters and scope of winnowing system were established. Based on Box-Behnken’s central combination design theory, response surface experiment was carried out to analyze the influence of various factors on winnowing loss rate and impurity rate and influencing factors. The experimental results showed that the significant order of influence of air separation loss rate was impurity suction height, cross-flow fan speed and seedling suction height. The remarkable order of impurity content was cross-flow fan speed, impurity suction height and seedling suction height. The optimal parameter combination was as follows: cross-flow fan speed of 1508r/min, seedling suction height of 181mm and impurity suction height of 211mm, and the corresponding air separation loss rate and impurity content were 1.52% and 1.01%. Compared with that before optimization, it was decreased by 1.42 percentage points and 1.26 percentage points, respectively. The research results could provide reference for the research of air separation system of peanut picking and harvesting machine. This experiment was based on the air separation system of axial-flow peanut full-feeding harvester, and the experiment object was only “Shanhua 9”. It was suggested that the performance of different peanut varieties and harvesting equipment with different structures should be discussed in depth.