The control approaches for a continuous two stage mixed suspension mixed product removal (MSMPR) cascade crystallizer are studied in this work. Both cooling and antisolvent addition are applied at both stages to manipulate the process. Considering both crystal size and yield as controlled variables, the attainable region of crystal size and yield is obtained. Two advanced control schemes are discussed: (1) decentralized proportional-integral-derivative (PID) control; and (2) nonlinear model predictive control (NMPC). While decentralized PID control framework is proved to require change of control structure when a relatively large operating region is essential, nonlinear model predictive control scheme shows superior performance for fast target product property change over and disturbance rejection. (C) 2015 Elsevier Ltd. All rights reserved.