The organic Rankine cycle (ORC) is a popular and promising technology that has been widely studied and adopted in renewable and sustainable energy utilization and low-grade waste heat recovery. The use of zeotropic mixtures in ORC has been attracting more and more attention because of the possibility to match the temperature profile of the heat source by non-isothermal phase change, which reduces the irreversibility in the evaporator and the condenser. The selection of working fluid and expander is strongly interconnected. As a novel expander, a single screw expander was selected and used in this paper for efficient utilization of the wet zeotropic mixtures listed in REFPROP 9.1 in a low-temperature subcritical ORC system. Five indicators, namely net work, thermal efficiency, heat exchange load of condenser, temperature glide in evaporator, and temperature glide in condenser, were used to analyze the performance of an ORC system with wet and isentropic zeotropic mixtures as working fluids. The calculation and analysis results indicate that R441A with an expander outlet temperature of 320 K may be the suitable zeotropic mixture used for both open and close type heat source. R436B may be selected with an expander outlet temperature of 315 K. R432A may be selected with an expander outlet temperature from 295 K to 310 K.