Multistage Flash Desalination (MSF) is currently facing an enormous challenge in cutting of the cost: within the last few years, the MSF experienced a gradual decline in investment compared to other techniques of desalting water and thus, a significant improvement is required to remain attractive for capital investors. Improved process control is a cost effective approach to energy conservation and increased process profitability. In this work, a dynamic model is presented using gPROMS model builder to optimize and control MSF process. The Proportional Integral Derivative controller (PID) and Generic Model Control (GMC) are used successfully to control the Top brine temperature (TBT) and the brine level (BL) in the last stage at different times of the year. The objectives of this study are: firstly, to obtain optimum TBT and BL profiles for four different seasons throughout the year by minimizing the Total Seasonal Operating Cost (TSOC); secondly, to track the optimum TBT and BL profiles using PID and GMC controllers with and without the presence of constraints; thirdly, to examine how both types of controllers handle the disturbances which occur in the plant. The results are promising and show that GMC controller provides better performance over conventional PID controller to handle a nonlinear system. (C) 2016 Elsevier Ltd. All rights reserved.