The　organic　Rankine　cycle　(ORC)　is　a　popular　technology　used　in　waste　heat　recovery　and　medium-low-temperature　heat　utilization.　Working　fluid　plays　a　very　important　role　in　ORC.　The　selection　of　working　fluid　can　greatly　affect　the　efficiency,　the　operation　condition,　the　impact　on　the　environment,　and　the　economic　feasibility　of　ORC.　The　expander　is　a　key　device　in　ORC.　As　a　novel　expander,　single-screw　expanders　have　been　becoming　a　research　focus　in　the　above　two　areas　because　of　their　many　good　characteristics.　One　of　the　advantages　of　single-screw　configurations　is　that　they　can　conduct　a　vapor-liquid　two-phase　expansion.　Therefore,　in　order　to　give　full　play　to　this　advantage,　a　working　fluid　selection　for　ORC　using　a　single-screw　expander　was　conducted　in　this　paper.　Three　indicators,　namely,　net　work　output,　thermal　efficiency,　and　heat　exchange　load　of　condenser,　were　used　to　analyze　the　performance　of　an　ORC　system.　Through　calculation　and　analysis,　it　can　be　seen　that　an　ORC　system　that　uses　a　single-screw　expander　and　undergoes　a　vapor-liquid　two-phase　expansion　is　able　to　obtain　a　higher　thermal　efficiency,　higher　net　work　output,　and　a　smaller　heat　exchange　load　of　the　condenser.　Regardless　of　whether　isentropic　efficiency　of　the　expander　is　considered　or　not,　cis-butene　may　be　the　best　candidate　for　working　in　subcritical　cycles.　HFO　working　fluids　are　more　suitable　for　working　in　transcritical　cycles,　and　HFO-1234ze(E)　may　be　the　best.