Numerical simulation of the corn starch granule dynamics were performed by software of computational fluid mechanics to characterize the separation performance and separation process of hydrocyclone. The effects of parameters such as inlet velocity, split ratio, and feed concentration on separation efficiency of hydrocyclone were compared and analyzed, and the volume fraction distribution of different size starch granules in hydrocyclone was investigated. The response surface methodology (RSM) analysis of Box-Behnken experimental design to optimize parameters. The influence of inlet velocity, split ratio, and feed concentration on hydrocyclone separation efficiency were measured, and quadratic regression equations were constructed to examine the optimization parameter. The results indicated that the inlet velocity, split ratio, and feed concentration had an effect on the separation efficiency of the corn starch and order of effect as followed: split ratio＞feed concentration＞inlet velocity, and could be adjusted properly to improve the separation efficiency of hydrocyclone. The optimum parameter condtion was as followed: inlet velocity was 8 m/s, split ratio was 5%, feed concentration was 12%. Under the optimal parameter condition, the separation efficiency of hydrocyclone was 98.84%.