This works tudies the optimization of regenerative gas compression refrigeration systems, where the entransy dissipation analysis and thermodynamic analysis are made to establish the mathematical relation between the intermediate temperatures and the design parameters, as well as the constraints of each design parameter. These relations are used to construct the mathematical model of the optimization problem in terms of the conditional extremum method, and the solution gives the optimal values of design parameters simultaneously. Taking the overall thermal conductance minimization of a regenerative refrigerator as an example, the results show that the minimum overall thermal conductance exists for fixed cooling requirements, running cost, and pressure ratio. Furthermore, the minimum overall thermal conductance decreases for the increase of themass flow rate of the hot-end fluidor the pressure ratio, whereas first decreases and then increases for the increase of the net power consumption.