A gradient SMB model is used to analyze the separation performance of proteins in a step-wise salt gradient ion-exchange simulated moving bed (IE-SMB) for the nonlinear adsorption equilibrium isotherms. The strategy of the selection of salt gradient in IE-SMB chromatography is discussed based on the adsorption equilibrium isotherms of both BSA and myoglobin on Q-Sepharose FF anion exchanger in the pH 8 Tris buffer. The separation region is used to select the flow rates in the salt gradient IE-SMB chromatography for the separation of proteins. The separation region is calculated by the gradient SMB model where both the mass transfer resistance in the ion exchangers and axial liquid dispersion in columns are taken into account. Some strategies are suggested for the selections of salt gradient and flow rates in the IE-SMB chromatography with open loop configuration for two cases: (a) binary separation of proteins with the requirement of the complete recovery from extract stream and raffinate stream; and (b) protein purification from a stream with some impurities.