Among the multitude of combinational rules for determining potential parameters of the energy of intermolecular interaction of mixtures only those that satisfy two condition are distinguished by high reliability: 1) dependence on the composition of mixtures is strictly justified; 2) potential parameters are associated with coordinates of the characteristic point on the surface of state, which allows you to monitor the results obtained. This paper proposes a method for calculating potential parameters that for any model potential are uniquely related to the coordinates of a Boyle’s point: temperature TB and Boyle volume —ТB(dB/dT)B. The resulting dependence on the composition strictly follows from dependence on the composition of the second virial coefficient of the mixture. The method allows to determine the potential parameters of the mixtures of a arbitrary composition only the basis of data for pure components.