One way to increase the thermal efficiency of vehicle diesel engines is to recover waste heat by using an organic Rankine cycle (ORC) system. Tests were conducted to study the running performances of diesel engines in the whole operating range. The law of variation of the exhaust energy rate under various engine operating conditions was also analyzed. A diesel engine-ORC combined system was designed, and relevant evaluation indexes proposed. The variation of the running performances of the combined system under various engine operating conditions was investigated. R245fa and R152a were selected as the components of the mixed working fluid. Thereafter, six kinds of mixed working fluids with different compositions were presented. The effects of mixed working fluids with different compositions on the running performances of the combined system were revealed. Results show that the running performances of the combined system can be improved effectively when mass fraction R152a in the mixed working fluid is high and the engine operates with high power. For the mixed working fluid M1 (R245fa/R152a, 0.1/0.9, by mass fraction), the net power output of the combined system reaches the maximum of 34.61 kW. Output energy density of working fluid (OEDWF), waste heat recovery efficiency (WHRE), and engine thermal efficiency increasing ratio (ETEIR) all reach their maximum values at 42.7 kJ/kg, 10.90%, and 11.29%, respectively.