Eight kinds of cycle media in organic Rankine cycle(ORC) were compared during the thermodynamic process.Considering the systemic,reliable and environmental factors,R245fa was the optimum selection for ORC.For the application of Cummins heavy duty vehicle engine,the power generation system with the waste heat recovery was designed.Recovering the heat from charge air,tail pipe gas and exhaust gas,the power generation was realized.The efficiency of waste heat recovery in the system was 10.4%.