Aiming at the problems of long development cycle and low design efficiency in the process of agricultural machinery product design and development, an intelligent design and optimization system for cleaning device of rice and wheat combine harvester was constructed. The system was composed of user demand module, knowledge base and inference engine module, parametric modeling module and intelligent optimization module, which can realize the design and optimization of cleaning device. Firstly, the design knowledge base of cleaning device in SQL Server 2012 was established, and the inference engine of cleaning device design was studied. According to the user’s design requirements, combined with the established knowledge base and inference engine module of cleaning device design, the relevant design knowledge in the knowledge base was called, and the reference method based on case and rule was used for designing, so as to output the parameters of key parts of cleaning device. Secondly, NX was redeveloped in Visual Studio programming software, which combined the two development languages, C++ and KF (knowledge fusion). In this way, the parametric model library of cleaning device was built, and then some key parts of cleaning device could be built rapidly in this library. Thirdly, the orthogonal tests of the CFD-EDEM coupling simulation of the cleaning device were designed with the air inlet velocity of the cleaning device, the inclination angle of the upper air guide plate, the inclination angle of the lower air guide plate and the vibration screen frequency as optimization variables. The cleaning impurity rate and loss rate in the test process were calculated to evaluate the cleaning effect. Finally, based on the simulation data, PSO-SVR algorithm was used to construct the regression model of the optimization variables, the cleaning impurity rate and the cleaning loss rate. After that, the SPEA2 algorithm was used to realize the multi-objective optimization of the cleaning impurity rate and loss rate, and to obtain a set of Pareto non-inferior solution. The results showed that when the wind speed at the air inlet of the cleaning device was 6m/s, the frequency of the vibrating screen was 4.5Hz, the inclination angle of the upper air guide plate was 32° and the inclination angle of the lower air guide plate was 18°, the impurity content and loss rate of the corresponding cleaning device model were 1.077% and 0.97%, respectively. As a reference, the model design parameters of key parts of the cleaning device can be optimized, which provided an optimization scheme for the design process.