Organic Rankine Cycle (ORC) could be used to recover low-grade waste heat. When a vehicle is running, the engine exhaust gas states have a wide range of variance. Defining the operational conditions of the ORC that achieve the maximum utilization of waste heat is important. In this paper the performance of different working fluids operating in specific regions was analyzed using a thermodynamic model built in Matlab together with REFPROP. Nine different pure organic working fluids were selected according to their physical and chemical properties. The results were compared in the regions when net power outputs were fixed at 10 kW. Safety levels and environmental impacts were also evaluated. The outcomes indicate that R11, R141b, R113 and R123 manifest slightly higher thermodynamic performances than the others; however, R245fa and R245ca are the most environment-friendly working fluids for engine waste heat-recovery applications. The optimal control principle of ORC under the transient process is discussed based on the analytical results.