On the basis of analyzing the characteristics of epikarst "dualistic" water resource in Karst Region, the author combines the set pair analysis method with entropy weight method to establish entropy weight set pair coupling evaluation model.The author takes Guizhou Province as the typical karst distribution area for an example, and analyzes the safety condition of epikarst water resource in karst region from 2000 to 2008.The result shows that the water source of Guizhou Province was in an unsafe state from 2000 to 2004, and in safer state from 2005 to 2008.