Abstract: Based on PSR conceptual framework, the evaluation index system of groundwater resources vulnerability is constructed and the groundwater resource vulnerability in karst region of Guizhou Province is evaluated using the methods of grey correlation weighting and the matter-element analysis. Following conclusions can be drawn: firstly, groundwater resources vulnerability in Karst region is impacted by the natural environment, especially the rainfall; the agricultural non-point source pollution and the deterioration of agricultural ecological environment are main direct controlling factors of the groundwater resources vulnerability. Secondly, for recent nine years, the stress vulnerability of groundwater resources vulnerability is at "fragile", "medium fragile" and "fragile" levels and the state vulnerability remains at "fragile" level, which indicates that vulnerability mainly comes from stress. Thirdly, in general, the groundwater resources vulnerability in karst region of Guizhou Province is good, but fluctuant; the influence of drought disaster on groundwater resources vulnerability in karst region is relatively big; overall correlation is less than zero and with vulnerability risk, so optimistic opinion should not be adopted.