Organic Rankine cycle (ORC) is applicable for the heat-work conversion. Whereas, there also exist a lot issues that influence the efficiency and the cost of the system. In this work, eleven pure working fluids (as categorized into alkanes, and fluorinated alkanes) are investigated based on the first and second law of thermodynamics. The major objective is to obtain the most suitable working fluid for the latent heat source. The results show that the working fluid is an important factor of the system performance. The heat absorption of the working fluid in the evaporator is inversely proportional to the evaporating temperature, but the thermal and exergetic efficiencies are just the opposite. RC318 has the highest net power output and the lowest outlet temperature of the heat source, but its global warming potential (GWP) value is too high. The cyclohexane shows the highest thermal efficiency among the fluids investigated. Moreover, the figure of merit (FOM) of the isobutane is higher than that of other working fluids. Overall, the cyclohexane shows that the optimal comprehensive performance is more feasible for medium grade heat source in engineering applications.