It is of great significance to perform performance analysis and optimization of regenerative supercritical carbon dioxide (S-CO2) Brayton cycle because it has great development and application potential in the field of gas turbines waste heat recovery and utilization. In this paper, the theory of finite-time thermodynamics is used to establish a regenerative S-CO2 Brayton cycle model with various irreversible factors including the heat transfer with finite temperature difference, the irreversible compression and the irreversible expansion under the condition of variable-temperature heat source. Then, the influences of working fluids mass flow rate, turbine and compressor efficiencies, and total heat exchanger inventory on the characteristic relationship between the exergy efficiency and the cycle pressure ratio are analyzed. Finally, by choosing the maximum exergy efficiency at fixed total heat exchanger inventory as the optimization objective, the heat conductance distribution ratios of the heater, the cooler and rege-nerator, as well as the mass flow rate of the working fluid and the cycle pressure ratio, are optimized. The results show that, within the parameter value ranges chosen in this paper, the optimized exergy efficiency increases by 37.96%, as compared with the initial design value. The design parameters corresponding to the maximum exergy efficiencies at different working fluid mass flow rates are also given.