Mountain depopulation is a worldwide phenomenon observed in all continents. It has varied socioeconomic reasons; among others, the low profitability of traditional agriculture, the better job possibilities and the higher level of services in urban settlements. However, it is often recognized that depopulation is related to natural factors such as elevation, slope or lithology. It is also observed that protected areas are frequently established in depopulated mountain regions. Their primary aim is the conservation of nature, but they may help tourism development as well. Tourism, in turn, may slow down or even reverse the process of depopulation. In this study, we investigate the impact of topographic and lithologic factors, namely of karst settings, on mountain demographic processes and the relationship of protected areas and tourism through the example of the northern part of Zlatibor District (Western Serbia). The study area is characterized by mountains and hills at elevations from 200 to 1600 m a.s.l. Our aim is to find GIS-based statistical relationships between topographic, lithologic factors and demographic characteristics. In this area, mountain depopulation started after WWII, and we proved that this process was strongly controlled by topographic factors. The higher and more dissected the area, the more significant is the decrease of the population and the more advanced is the ageing. As a result, population density contrasts are much more pronounced now than 70 years ago. After WWII, depopulation and ageing became gradually more serious on karstic terrains than on non-karst. However, by using compound topographic and lithologic types, we proved that it is not the effect of karst, but the effect of topography. The flow of population from hills and mountains to valleys and basins are closely related to the restructuring of the economic sectors. At present, for the study area, the development of tourism is unequivocally naturebased and connected to protected areas, namely to Tara National Park, Zlatibor Nature Park and Šargan-Mokra Gora Nature Park. In this paper, we also demonstrate how lithology influences tourism possibilities. The leading role of Zlatibor in tourism development is largely thanks to its favourable position on a main transit route.