The phase separationphenomena or cloud points (CP) behaviorof nonionic octylphenol polyoxyethylene etherwith oxyethylene glycol ether unit of 15 (OP-15) were investigated in aqueous micellar solutions containinghigh concentrations of inorganic salts including NaCl, KCl, MgCl2, CaCl2, BaCl2, AlCl3, FeCl3, Na2SO4and Na2SiO3. The change in CP induced by salts and its mechanism are discussed theoretically. In aqueous solutionscontaining high concentration of salt, for thefirst time the linear relationship between CP and saltconcentrationiswellestablishedtocharacterizethedepressionofCP.Basedonpseudophaseseparationmodel,thermodynamic parameters are estimated and adopted to further describe the phase separation process andthe interactions between OP-15 molecules or the OP-15/water interactions. Thermodynamic parametersincluding standard Gibbs energy change (DG0CP), enthalpy change (DH0CP) and entropy change (DS0CP)indicate that the additions of different salts result in the change in entropy-driven nonspontaneousprocess of phase separation. These data, which are from the compensation temperatures and the changeof molar heat capacity, also prove that different ions induce the change in the interactions betweensurfactant molecules or the surfactant–water interaction and thus affect the depression of CP. Thesefindings help with understanding the effect of inorganic salts, especially the high concentration of salt, onCP of nonionic surfactant and then broadening the application of nonionic surfactant based on CP such asthe extraction of biomaterials in biological samples derived from animals or plants, etc.