Taking net power output as the optimization objective, the exergy loss distribution of the subcritical Organic Rankine Cycle (ORC) system by using R245fa as the working fluid was calculated under the optimal conditions. The influences of heat source temperature, the evaporator pinch point temperature difference, the expander isentropic efficiency and the cooling water temperature rise on the exergy loss distribution of subcritical ORC system are comprehensively discussed. It is found that there exists a critical value of expander isentropic efficiency and cooling water temperature rise, respectively, under certain conditions. The magnitude of critical value will affect the relative distribution of exergy loss in the expander, the evaporator and the condenser. The research results will help to better understand the characteristics of the exergy loss distribution in an ORC system.