Groundwater is an important drinking water source in Southwest China. However, there exists a large area of sulfate exceeding standard in groundwater in the northern part of Zhenning County in Central Guizhou Province, which leads to the problem of water shortage in local area. The following conclusions were obtained by methods of lithofacies palaeogeographic analysis, hydrochemical analysis, D, ¹⁸O, ³⁴S isotope test, rock sample test, core observation and other technical methods:The main source of water supply in the study area is meteoric water; the concentration of sulfate (SO₄^2-) in groundwater is in the range of 30-1100 mg/L, with an average value of 221.78 mg/L, showing the characteristics of highly enriched S0₄^2-; the concentration of S0₄^2- in different types of groundwater exhibits the law of well > rising spring > falling spring > karst pool > underground river > bedrock fissure spring > epikarst spring; the source of sulfate root in epikarst spring is mainly meteoric water, and the source of sulfate root in high sulfate samples such as J469, J585, ZK3-2 and C010 is mainly dissolved in gypsum. On such a basis and in combination with drilling data, the authors detected the distribution of gypsum rock layer and the characteristics of aquifer structure, and adopted the lower sulfate aquifers to obtain qualified drinking water source by establishing the "cross layer water finding" model, which can effectively solve the problem of water shortage in the study area.