In view of the composition characteristics of sodium sulfate subtype salt lake brine in Laguocuo, Xizang, and combined with local climate characteristics, the phase equilibria of reciprocal quinary system Li+, Na+, K+/Cl-, SO42--H2O, as well as all subsystems, were predicted under ten temperatures within the range of 248.15 similar to 348.15 K. The corresponding 3D phase diagrams were drawn, and the saturation projection planes and crystallization phase regions were disassembled and analyzed. The isothermal dissolution equilibrium method was used to study the stable phase equilibrium of two ternary subsystems (LiCl-NaCl-H2O and LiCl-KCl-H2O) in the temperature range of 253.15 to 348.15 K, and the comparison between experimental and calculated results verified the applicability of the model selected in this paper. Meanwhile, the isothermal evaporation routes of brine at different temperatures were predicted by using phase diagram of this reciprocal quinary system, and the rules of ion concentration and salt precipitation in liquid phase during isothermal evaporation were obtained. Based on theoretical predictions, and combined with local natural conditions, it is proposed to use multi-stage freezing to make mirabilite crystallize and precipitate from brine, reduce sulfate content in brine, change the composition of brine, and further to achieve comprehensive development and utilization of brine resources. Through the experiment of brine evaporation and theoretical calculations, the effects of freezing temperature and brine composition on solid phase compositions and sulfate removal rate were investigated, and a clean separation process of obtaining high-grade lithium and potassium salts was put forward. The research results of this paper will have important referential significance for guiding the development of brine resources in similar salt lakes.