Several areas in Balkans and Danube Basin countries are threatened by the widespread occurrence of desertification that could lead to severe degradations of the natural resources such as the impoverishment of soils, the deterioration of the biomass or even the reduction of the biodiversity. Some areas in Greece are already or likely to be affected by desertification and the present work aims at developing a model for the assessment of the desertification risk, using the prefecture of Kilkis as study case. The assessment methodology consists in combining various desertification indicators relative to the climate, vegetation, soils and management into a unique final index. The prior knowledge of the dominant processes acting in the region is integrated to the model by performing a multi-criteria analysis. The use of the GIS technique allowed an efficient processing of the collected data and the generation of relevant intermediate thematic maps and a final desertification risk map.