Lop Nur is located at the eastmost end of the Tarim Basin in Xinjiang, Northwestern China. This study reviews the hydrochemical characteristics and evolution of underground brine in Lop Nur, based on analytical data from 429 water samples (mainly brine). It is found that in the NE–SW direction, from the periphery to the Luobei sub-depression, while the hydrochemical type varies from the sodium sulfate subtype (S) to the magnesium sulfate subtype (M), the corresponding brine in the phase diagram transfers from the thenardite phase (Then) area, through the bloedite phase (Blo), epsomite phase (Eps), picromerite phase (Picro), finally reaching the sylvite phase (Syl) area. As for the degree of evolution, the sequence is the periphery < Luobei horizontally and the overlying glauberite brine < the underlying clastic brine vertically. It is concluded that the oxygen and hydrogen isotopic compositions of the brine have evidently been affected through the effects of evaporation and altitude, as well as the changes in local water circulation in recent years. Boron and chloride isotopic compositions show that the glauberite brine is formed under more arid conditions than the clastic one. The strontium isotopic composition indicates that the Lop Nur brine primarily originates from surface water; however, deep recharge may also be involved in the evolution of the brine, according to previous noble gas studies. It is confirmed that the brine in Lop Nur has become enriched with potassium prior to halite precipitation over the full course of the salt lake’s evolution. Based on chemical compositions of brine from drillhole LDK01 and previous lithological studies, the evolution of the salt lake can be divided into three stages and it is inferred that the brine in Lop Nur may have undergone at least two significant concentration-dilution periods.