In order to obtain grain moving laws in inertia separation chamber of combine harvester threshing prior to cutting, grains motion was simulated by using computational fluid dynamics and discrete element coupled methods. Simulation results showed that grain particles were separated from short straw through airflow and the performance of chamber separating and cleaning grain was improved with the increasing of airflow velocity, while the turbulence phenomenon in the rear of chamber got more serious and airflow pressure drop was increased. Not full grain particles also deposited in chamber. In order to verify the validity of simulation results, the experimental test was conducted. Experimental results and simulation results were basically accord, which showed that the simulation of grain motion in inertia separation chamber based on CFD-DEM was feasible. The results would be a better basis to improve the performance of inertia separation chamber to separate and clean grain.