Solubility isotherms as well as the corresponding solid phases of the quaternary system MgCl2+LiCl+NH4Cl+H2O at 298.15 K have been elaborately measured by an isothermal equilibrium method. Four crystallization fields including two double salts (LiCI.MgCl2 center dot 7H(2)O((s)) and NH4Cl center dot MgCl2 center dot 6H(2)O((s))), one hydrate salt (MgCl2 center dot 6H(2)O((s))), and one solid-solution (LiCl center dot H2O+NH4Cl)((ss)) were detected in this system. A Pitzer-Simoson-Clegg (PSC) thermodynamic model was used to simulate and predict the thermodynamic properties of this quaternary system and its subsystems. The water activities of the ternary systems MgCl2+LiCl+H2O and LiCl+NH4Cl+H2O, as well as the solubility of the quaternary system MgCl2+LiCl+NH4Cl+H2O, were predicted by the PSC model, the results of which were compared with available literature data and the experimental results in this work. The excellent agreement between the predicted and experimental results indicates that the solubility results obtained in this work are reliable. On the basis of the quaternary phase diagram calculated by the model, several examples are provided for industrial applications.