Groundwater plays an important role in ecological environment protection in arid and semi-arid areas. Therefore, understanding the characteristics of hydrochemical evolution is of great significance for the sustainable use of groundwater in the area of the Tailan River Basin. The Tailan River Basin is located in an arid, ecologically sensitive area in western China. In this study, we collected 42 groups of representative water samples from the Tailan River Basin and analyzed the chemical distribution in the groundwater using mathematical statistics, Piper and Gibbs diagrams, ion ratio analysis, and hydrogeochemical simulation methods. We also discussed the water–rock interactions in the groundwater hydrochemical evolutionary process. The results were as follows: (1) The chemical types of groundwater changed from HCO3·SO4-Ca·Na to SO4·Cl-Na·Ca, Cl·SO4-Na, and Cl-Na, and the total dissolved solids content increased from less than 1 g/L to more than 40 g/L from the gravel plain to the fine soil plain. (2) The Gibbs diagram, the ion ratio analysis, and the saturation index showed that the groundwater chemical characteristics in the study area were mainly controlled by water–rock interactions, as well as evaporation and concentration. Along the runoff of groundwater, halite and gypsum were dissolved. Nevertheless, dolomite and calcite precipitated. The relationship between the chlor-alkali index and [(Na+ + K+)-Cl−] and [(Ca2+ + Mg2+)-(HCO3− + SO42−)] indicated that cation exchange also affects the chemical composition of groundwater in the area. (3) Through reverse hydrogeochemical simulation, the main water–rock effect of the groundwater runoff process revealed by qualitative analysis was quantitatively verified.