There are abundant brine resources in the Balun Mahai Basin of Qaidam, but the genetic mechanism and potential of brine resources still need to be determined. This study focuses on the intercrystalline brine in the Balema Lake Basin, conducting geochemical research on elements and hydrogen-oxygen isotopes to systematically analyze its water source, solute origins, evolution process, and genesis model. The study also explores the mining potential of potassium, boron, and lithium elements. The results show that the intercrystalline brine in the northern part of the Balema Lake Basin is of the magnesium sulfate subtype, while the southern part predominantly features chloride water. The solutes in the brine mainly originate from the dissolution of halite, potassium salts, and gypsum. The water chemistry is controlled by evaporation, water-rock reactions, and cation exchange. The chloride-type water in the south may be influenced by deep Ca-Cl water flowing along faults. The water chemistry characteristics indicate that the intercrystalline brine is formed by halite dissolution, with low metamorphic degree and poor sealing in the salt-bearing layers. Hydrogen-oxygen isotopes show that the main water source of the intercrystalline brine is atmospheric precipitation or snowmelt from the Qilian Mountains, with the primary recharge sources being the Yuka River and shallow groundwater flowing through the alluvial fan. Strong evaporation and water-rock interactions have significantly impacted the formation of the brine deposits. The differences in water chemistry types and spatial distribution between the northern and southern regions are fundamentally related to the recharge and mixing of these two sources. The brine genesis can be summarized as a "dissolution recharge + deep recharge" dual mining model. The brine in the study area has considerable potential for potassium, boron, and lithium resources. Based on the comprehensive water chemistry characteristics, salt layer thickness, regional salt formation evolution process, drilling sites ZK7618, ZK8014, ZK8024, and ZK8431 are likely favorable targets for mineral exploration.