The performance of the ORC (organic Rankine cycle) systems using zeotropic mixtures as working fluids for recovering waste heat of flue gas from industrial boiler is examined on the basis of thermodynamics and thermo-economics under different operating conditions. In order to explore the potential of the mixtures as the working fluids in the ORC, the effects of various mixtures with different components and composition proportions on the system performance have been analyzed. The results show that the compositions of the mixtures have an important effect on the ORC system performance, which is associated with the temperature glide during the phase change of mixtures. From the point of thermodynamics, the performance of the ORC system is not always improved by employing the mixtures as the working fluids. The merit of the mixtures is related to the restrictive conditions of the ORC, different operating conditions results in different conclusions. At a fixed pinch point temperature difference, the small mean heat transfer temperature difference in heat exchangers will lead to a larger heat transfer area and the larger total cost of the ORC system. Compared with the ORC with pure working fluids, the ORC with the mixtures presents a poor economical performance.