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Groundwater is a valuable water source for drinking and irrigation purposes in semiarid regions. Groundwater pollution may affect human health if it is not pretreated and provided for human use. This study investigated the hydrochemical characteristics driving groundwater quality for drinking and irrigation purposes and potential human health risks in the Xinzhou Basin, Shanxi Province, North China. More specifically, we first investigated hydrochemical characteristics using a descriptive statistical analysis method. We then classified the hydrochemical types and analyzed the evolution mechanisms of groundwater using Piper and Gibbs diagrams. Finally, we appraised the groundwater quality for drinking and irrigation purposes using the entropy water quality index (EWQI). We assessed the associated human health risks for different age and sex groups through drinking intake and dermal contact pathways. Overall, we found that (1) Ca-HCO3 and Ca·Mg-HCO3 were the dominant hydrochemical types and were mainly governed by rock weathering and water–rock interactions. (2) Based on the EWQI classifications, 67.74% of the groundwater samples were classified as medium quality and acceptable for drinking purpose. According to the values of sodium adsorption ratio (SAR), residual sodium carbonate (RSC) and soluble sodium percentage (%Na), 90.32% of the samples were suitable for irrigation, while the remaining samples were unfit for irrigation because of the high salinity in the groundwater. (3) Some contaminants in the groundwater, such as NO3−, NO2− and F−, exceeded the standard limits and may cause potential risks to human health. Our work presented in this paper could establish reasonable management strategies for sustainable groundwater quality protection to protect public health.