Energy saving and environment protection are two most important issues that today’s internal combustion engine industry must tackle with. Lots of heat energy waste with the exhaust gas when the engine is running. Organic Rankine cycle (ORC) is a good method to recover the waste heat of the engine exhaust. In this paper, the mathematical model of ORC was built up in Matlab and the parameters were optimized using genetic algorithm (GA). Eight pure component organic working fluids were selected and compared. The results indicate that the evaporating pressure of the working fluid and the condensing temperature are two important parameters for ORC; the super heater also can enhance the system thermal efficiency slightly.