Although using zeotropic mixtures in the organic Rankine cycle (ORC) system can improve its performance,the selection of the mixture working fluid is still a great challenge due to the lack of selectioncriteria. In the present work, the thermodynamic selection criteria of zeotropic mixtures is proposed based on the exergy analysis of the subcritical ORC. The mixture composition can be directly determined according to the thermophysical properties of working fluids without massive thermodynamic calculation.The effect of temperature match between the working fluids and the heat source/sink on thesystem performance is analyzed. And the overall exergy efficiency is set as the optimization index. For the heat source without limit to the outlet temperature, the improvement of the temperature match in the evaporator exhibits more significant influence on the cycle performance than that in the condenser. Thus, the match condition with the heat source shoud be firstly satified when selecting working fluids. The proper temperature glide in the condenser can further improve the cycle performance. The‘wet’ mixtures have relatively lower cycle performance compare to ‘dry’ and ‘isentropic’ ones. The steps of using this selection criteria and a case study to validate it are also illustrated.