A model, influence of water and salt on vegetation (IWSV), was developed to evaluate their influence on plant species. The main function of this model was to calculate a comprehensive index value for evaluating the suitability of plant growth. This model consists of five explanatory variables (vadose zone moisture content, vadose zone salinity, vadose zone lithology, depth to the water table, and groundwater mineralization) and two response variables (plant species and their cover). A set of independent data on three plant species, Artemisia ordosica, Salix psammophila, and Carex enervis, which are dominant species in the Mu Us Desert of northern China, were used to validate the model. Validation results show an overall correct prediction for the distribution of these three species. The results demonstrated that the IWSV model can be a useful tool for groundwater management and nature conservation in a semi-arid desert region, especially for predicting the vegetation distribution in areas with groundwater extraction.