The fluctuation of heat source conditions results in off-design operation of the radial inflow turbines (RIT) in the organic Rankine cycle. However, the flow loss characteristics of RIT under off-design conditions have not been completely revealed. The entropy production theory has the advantage of determining the quantity and location of energy dissipation, which is used to evaluate the energy loss of RIT under different conditions. In addition, the order of operating parameters on the RIT energy loss is determined by the orthogonal experimental method. The results show that each entropy production term and the entropy production of different components increase with the increase in the inlet pressure and inlet temperature, while they decrease with the increase in the outlet pressure of the RIT. Under different operating conditions, the turbulent dissipation and wall dissipation are the main cause of RIT energy loss, which are closely related to vortices and high velocity gradients in the flow field. The rotor and diffuser contribute the main energy loss of RIT. However, the volume-average entropy production and area-average entropy production of the stator and rotor are higher than those of other components. In addition, the wall shear is the main cause of the stator energy loss, while the turbulent dissipation dominants the rotor energy loss. The outlet pressure has the greatest impact on the turbulent entropy production and wall dissipation.