The Quaternary Lop Nor playa is the largest production base of potassium sulfate in the world. It has a mining history of more than 10 years, and its share in the Chinese potassium sulfate market is about 50% to-date. In this basin, the high-salinity potassium-rich brines are mainly contained in Middle Pleistocene-Holocene glauberite strata. Based on the monitoring of the underground brine table and geochemical analysis, this study reveals variations in the underground brine table and potassium-bearing grade before and after large-scale mining in the Lop Nor potash deposit. The results showed that the underground brine table and potassium sulfate grade decreased by varying degrees over sub-mineral areas after large-scale mining. The underground brine table declined by 8.5 m, on average, in the Luobei depression, by 6.4 m in the Tenglong platform and by 1.9 m in the Xinqing platform. However, the potassium-bearing grade showed the different trend. The Tenglong platform had the largest decline with average decreases in layers W1, W2 and W3 of 18.2%, 13.0% and 24.8%, respectively. In the Xinqing platform, the average decrease in layersW2 and W3 were 17.4% and 16.0% respectively. The Luobei depression decreases were relatively small (W1, W2 and W3 decreased 4.3%, 4.2% and 3.1%, respectively). This research provides a theoretical basis for the rational development and sustainable use of the potassium-rich brines in the Lop Nor basin.