Hydrochemical processes under intense human activities were explored on the basis of the hydrochemical characteristics of 109 surface water samples and 129 groundwater samples collected during August 2015 to September 2016, in the Kaidu River Basin. Results obtained in this study indicated that the water in the basin was neutral to slightly alkaline with low total dissolved solids. Rock weathering and evaporation controlled the natural hydrochemical mechanisms. Mountain groundwater and stream water were dominated by Ca²⁺-HCO₃⁻ type water, whereas the plains groundwater was dominated by mixed type water. The results of principal component analysis demonstrated that water-rock interaction and human activity explained 71.6% and 12.9% of surface water hydrochemical variations, respectively, and 75.1% and 14.2% of groundwater hydrochemical variations, respectively. Sulfate, chloride, and carbonate weathering were the major water-rock interaction processes. Livestock farming and agricultural activities were the primary human activities influencing the water hydrochemistry. In addition, cation exchange is another important process influencing the hydrochemical characteristics in the study area. This study would be helpful in forecasting of water quality in arid areas.