The temperature of outlet fluid of the heat exchanger system is controlled with Artificial Neural Network Based Model Reference (ANNBMR) control method. The ANNBMR controller designed arranges the temperature of the outlet fluid to reach a desired reference value in the shortest possible time, despite the flow and temperature variation of input fluid. The simulation of ANNBMR controller designed with the use of the plant model of the heat exchanger system is carried out in MATLAB Simulink and simulation results are obtained. The simulations results of the proposed ANNBMR controller is compared with the simulations results of the PID conventional controller. The proposed controller shows better performance and reduces both settling time and maximum overshoot and by shortening the error signal between the input and output in a shorter period of time. The obtained simulation results prove that the proposed control method is quite successful.