Pressure relief system is a system to prevent overpressure inside protected equipment that exceeds its maximum allowable working pressure (MAWP) to disposal treatment. Relief system is designed on two different plant case studies, which are dimethyl-ether and ethylbenzene plants by using conventional design procedure. Nevertheless, the conventional design steps are not considering cost optimization of plant installed with relief system. Thus, the design pressure of protected equipment, piping diameter, and disposal treatment is set to be manipulated variables to determine the cost minimization. Pressure drops of inlet piping and backpressure are as constraint variables due to standard requirements. The standards state that inlet piping pressure drops should be below 3% of set pressure and outlet piping pressure drop to set pressure percentage based on range to determined types of the relief valve to be used. From that, optimum plant design with consideration of pressure relief system’s installation can be achieved by calculating the total cost of plant designed with relief system when set pressures are changed. As a result, dimethyl-ether plant shows a minimum point of the total cost at 170% of set pressure increment, which is lower than its original design. On the other hand, ethylbenzene plant gives optimum point at original design as the total cost is higher at set pressure increment.