In this study, a three-level Box–Behnken factorial design combined with response surface methodology for modeling and optimizing of operation parameters of hydrocyclones, namely feed solid, inlet pressure, vortex diameter and apex diameter, to produce three group bentonite concentrates was developed. In order to produce bentonite concentrates, mathematical model equations were derived by computer simulation programming applying the least squares method using Minitab 15 software. Second-order response functions were produced for the cation exchange capacity (CEC), free swelling volume (FSV) and apparent viscosity (AV) of bentonite concentrates. Predicted values are in good agreement with experimental values. After hydrocyclone separation the CEC increased by 138%, the FSV by 194% and AV by 325% in the bentonites, which in their natural state are not suitable for industrial use. Additionally, this study has shown that the Box–Behnken and response surface methodology could be applied efficiently for the modeling of hydrocyclone separation of bentonite and it is an economically efficient way to obtain the maximum amount of information in a short period of time and with the minimum number of experiments.