A carbon dioxide (CO2) based mixture was investigated as a promising solution to improve system performance and expand the condensation temperature range of a CO2 transcritical Rankine cycle (C-TRC). An experimental study of TRC using CO2/R134a mixtures was performed to recover waste heat of engine coolant and exhaust gas from a heavy-duty diesel engine. The main purpose of this study was to investigate experimentally the effect of the composition ratio of CO2/R134a mixtures on system performance. Four CO2/R134a mixtures with mass composition ratios of 0.85/0.15, 0.7/0.3, 0.6/0.4 and 0.4/0.6 were selected. The high temperature working fluid was expanded through an expansion valve and then no power was produced. Thus, current research focused on the analysis of measured operating parameters and heat exchanger performance. Heat transfer coefficients of various heat exchangers using supercritical CO2/R134a mixtures were provided and discussed. These data may provide useful reference for cycle optimization and heat exchanger design in application of CO2 mixtures. Finally, the potential of power output was estimated numerically. Assuming an expander efficiency of 0.7, the maximum estimations of net power output using CO2/R134a (0.85/0.15), CO2/R134a (0.7/0.3), CO2/R134a (0.6/0.4) and CO2/R134a (0.4/0.6) are 5.07 kW, 5.45 kW, 5.30 kW, and 4.41 kW, respectively. Along with the increase of R134a composition, the estimation of net power output, thermal efficiency and exergy efficiency increased at first and then decreased. CO2/R134a (0.7/0.3) achieved the maximum net power output at a high expansion inlet pressure, while CO2/R134a (0.6/0.4) behaves better at low pressure.