<p>Quantitative evaluations on water resources safety in karst areas play a vital role in formulating reasonable water-resources devel policies, boosting the sustainability of water resources and implementing sustainable socioeconomic improvement. Therefore, on the basis of special characteristics of hydrology and water resources in karst regions of southwestern China, this study built an assessing indicator framework of water resources safety from five levels: Water resources occurring (WRO), Water environment condition (WEC), “Engineering” water scarcity (EWS), Water resources utilization (WRU) and Water resources management (WRM). Combination weights of assessing indicators were obtained through analytic hierarchy process (AHP) and entropy weight method, and an assessing model of water resources safety in karst regions was constructed on account of the coupling of analytical comparison method and alterable vague sets method. Taking Guiyang as an example, the water resources safety situation of Guiyang from 2013 to 2022 was evaluated by using this model and its main obstacle factors were explored. Results indicate that water resources safety level in Guiyang is on the rise, and the safety level rises from unsafe level to relatively safe level. Water resources utilization (WRU) is the essential factor affecting water resources safety in Guiyang. Total water resources volume, water yielding modulus, consumptive use of water per 10,000 Yuan GDP and exploitation and utilization rate of water resources are primary obstacle factors to the amelioration of water resources safety level. The assessing model can impersonally reflect time evolution characteristics and dominating constraints of water resources safety in karst regions, and assessing results are close to the actual situation, which can provide an effective, feasible and intuitive method for water resources safety evaluation in karst areas.</p>