In population studies, investigating the spatial distribution pattern of the population is considered as one of the important issues that can be discussed at the level of watersheds. The importance of the distribution pattern of population and human resources in the catchment area comes from the fact that human and population forces interact with each other in their geographical and environmental context, the effects of which, if not in their reasonable logic, will endanger human societies and the environment. The purpose of this research was to investigate the effect of different factors on population distribution patterns and probable vulnerabilities on the population of the watersheds using the capabilities of the spatial information system (GIS). The watershed of Qornuko, located in south of East Azarbaijan province-Iran, was selected as a study area. Based on the research methodology, at first, by reviewing the sources, the most important factors affecting the distribution of population were identified and then data and spatial information related to these factors along with demographic data were collected for the study area. The data used in this research included area map, village's location, topographic map (1/25000), Digital Elevation Model (DEM), rainfall, land use, waterways, roads, faults, landslide and demographic data of 1996, 2006 and 2011 years, which were used to extract required information. Different functions of GIS were used for spatial processing, and statistical processing was done in a spreadsheet environment. Based on the results, over time, the population of mountainous and steep areas decreased while the population of the plain areas was increased. Also, the distance between the villages and waterways has increased, the number of villages and population in the areas with slopes and landslides have reduced, and generally the population and the villages of the area removed from the vulnerable areas. Although the majority of the population in the study area is safe from the dangers of the fault, however, about 36% of the population must be protected against the possible risks of an earthquake resulting from the fault. In general, the process of population changes in the area has mainly been resulted to reduce the threats posed by natural and geomorphologic factors. It seems that there has been a form of compromise between the population of the watershed and its natural factors in order to preserve life and the possibility of utilizing of the study area resources. In addition, it seems that the influence of some factors such as topography and rainfall in the pattern of population distribution in many areas is common and to a large extent predictable, but the situation of the establishment of some villages and population in comparison to some Threat factors (environmental and non-environmental) such as faults, the distance from the streams and landslides, vary from area to area and shows more uncertainty. Therefore, in order to identify and control possible effects on the population due to vital factors such as fault and landslide, etc., the necessity of performing special studies for each watershed is inevitable and should be included in the stabilization watersheds plans. At the end, a vulnerability zoning map for the villages of the watershed areas has been suggested to the interested people in relation to the natural and abnormal factors based on advanced methods such as fuzzy inference system.