Heat integration plays a significant role in efficient operation of chemical processes and industrial plants and brings along considerable economic benefits. Heat exchanger networks are the platforms through which heat integration is usually implemented. Since heat exchanger networks interconnect different units of a process or even sometimes different companies, their control problem is an essential issue. In this paper a procedure is introduced for developing an effective control structure of the heat exchanger network to handle the fluctuations and changes in operating conditions. The novelty of the proposed method lies on the exergy-based formulation of the problem that uses the advantage of exergy analysis in quantifying the thermodynamic inefficiencies of heat exchangers and mixers. Analysing the control system in this study addresses the problem of calculating values for manipulated variables in order to maintain target temperatures and minimize inefficiencies. Two optimization problems were solved and compared, in order to illustrate the advantage of exergy analysis in describing the performance of the system.