The strip of the Depresión Central (Central Depresion) in northern Chile, between latitudes 24-25o S, is in the arid core of the Desierto de Atacama (Atacama Desert). This area is characterized by air humidity close to zero, which is the origin of scarce precipitations and consequently very small surface runoff. Despite this, some small springs (more or less permanent seepages) outflow in the western slope of Cordillera de Domeyko (Domeyco Range), to the west of the Depresión Central. This shows up that there is groundwater, which the low parts of the basins is accessed by some mining companies. To understand this groundwater system, a hydrogeochemical model is needed, allowing the identification of the origin of solutes in groundwater. Groundwater salinity varies from medium mineralization to highly saline. The present research is based on the major ions and several isotopes (87Sr/86Sr, δ34S (SO4), δ18O (SO4)) of groundwater samples. The research has identified a mineral soluble contribution in atmospheric dust originating from salts found in the Depresión Central. The contribution of this dust affects the chemical fingerprint of meteoric water precipitating in the high areas of the Cordillera de Domeyko. The study excludes a marine aerosol contribution to this area. Solute concentration and the ratio Cl/Br have pointed out the significant evapotranspiration processes, discarding halite dissolution. The isotopic variations allow identifying 3 possible geological units involved in water-rock interaction processes. In the central strip of the Cordillera de Domeyko water flows through intensely fractured Permian volcanic rocks, where the chemical fingerprint is close to recharge water, which along the downward flow path leach the eolian salts and dust in the Cordillera de Domeyko slope. There, groundwater acquires the rock radiogenic fingerprint, while the main source of sulphate comes probably from atmospheric dust. Below 3400 m asl, strontium isotopic composition changes, showing a low radiogenic strontium source, probably associated to the marine origin Jurassic carbonates existing in this area, which are easy to dissolve in this environment under favorable conditions. While the isotopic fingerprint of sulphur and oxygen in sulphate point to a probable relationship with kinetic oxidation of sulphides or native sulphur, coming from previous diagenetic processes and that can be associated to the stinking carbonates in this geological unit. Groundwater in the most distal areas of the Cordillera de Domeyko are possibly related to a mixture with salts in the formation Gravas de Atacama (Atacama Gravels) existing in this area. This will support the idea that a local remobilization through the dust entrained by the wind from the Depresión Central to higher elevation areas.