The organic Rankine cycle (ORC) is a popular technology used in waste heat recovery and low-grade heat utilization, which are two important measures to solve the problems brought by the energy crisis. The economic performance of ORC system is an important factor affecting its application and development. Therefore, the economic analysis of ORC is of great significance. In this study, R123 and R245fa, two frequently-used working fluids during the transition period, were selected for calculating and analyzing the economic performance of an ORC used for recovery of waste heat with a low flow rate and medium-low temperature. Five traditional economic indicators, namely total cost, net earnings, payback period, return on investment, levelized energy cost, and present value of total profit in system service life, which is a relatively new indicator, were used to establish the economic analysis model of ORC. The variation effects of evaporation temperature, condensation temperature of working fluid, flue gas inlet temperature, and mass flow rate of flue gas on the above six economic indicators were analyzed. The results show that the optimal evaporation temperature of R123 is 125 °C, the optimal condensation temperature is 33 °C, and the optimal heat source temperature is 217 °C. For R245fa, the optimal evaporation temperature is 122 °C, the optimal condensation temperature is 27 °C, and the optimal heat source temperature is 177 °C. The economic performance of an ORC demonstration project was reported and used for comparison with the estimation and analysis. It was found that the single screw expander has an excellent economy performance, which greatly reduces the proportion of expander cost in the ORC system.