Many investigations showed that the dependence of the separation performance of nanofiltration (NF) membrane for the single salt with Mg2+ or Ca2+ on the salt concentration was distinguished from that for the salt with Na+ or K+. In this paper, the results of the permeation experiments of some single salt solutions with M2+ or Ca2+ through ESNA 1 membrane showed that their observed transmission decreased with the growth of the concentration. This phenomenon is explained by the counter-ion adsorption of Mg2+ or Ca2+ on the surface of NF membrane. In order to evaluate the separation performance of NF membranes for the mixed salts solution with Mg2+ and Ca2+, the regulation coefficient was added in the model proposed in our preceding paper. A simple empirical equation was built to calculate the regulation coefficient at the different mixed salts solutions with Mg2+ and Ca2+. The empirical parameters were obtained on the basis of the permeation experiments of two type of binary salts solutions ((1) Na+, Mg2+ and Cl-; (2) Na+, Ca2+ and Cl-) though three kinds of NF membranes (ESNA 1-LF, ESNA 1 and LES 90). The regulation coefficient decreased with the growth of the total concentration of mixed salts and increased with the growth of the equivalent fraction of Mg2+ and Ca2+. The effect of the counter-ion adsorption of Ca2+ on the effective fixed charge density of NF membrane was more remarkable than that of Mg2+. Finally some complex mixed salts solutions with Mg2+ and Ca2+ were chosen to verify the model with the regulation coefficient. The model evaluation results of the observed transmission of each ion in the mixed salts solution with Mg2+ and Ca2+ through ESNA 1-LF, ESNA 1 and LES 90 membranes agreed quite well with the experimental data. The deviation between the model evaluation results and the experimental data of most ions was less than 20% for the case of ESNA 1-LF and LES 90, which of ESNA 1 membrane was less than 10%. (c) 2006 Elsevier B.V. All rights reserved.