The interactive effects of natural and human factors on ecosystem have been focused on by quite a few researchers. Many theories and methods were proposed to carry out such research work, but few researches focused on the quantitative assessment on large-scale ecological vulnerability caused by natural and human factors and indicated the difference between nature- and human-induced vulnerability. Taking Xijiang River Economic Belt in Guangxi (XREB for short) as a case area, we carried out assessment on vulnerability based on VSD model developed by Polsky and his cooperators in 2007. Five kinds of ecological vulnerable zones were divided accordingly. XREB is a naturally vulnerable region, and recent rapid development intensified the vulnerability. Our indices were composed of three sub-objects, ten elements and 25 indicators, which included factors from both natural and human aspects. Assessment and zoning results based on VSD model indicated the spatial differentiation of zones with different vulnerability, and zones with the lowest, lower, middle, higher and highest vulnerability occupied 11.31%, 22.63%, 27.60%, 24.39%, and 14.07%, respectively. The eastern and western parts of XREB were more vulnerable than the middle part. Vulnerable zones caused by natural factors including high elevation and complicated topography distributed in the mountain areas, but that caused by human activities distributed in the surrounding areas of big cities mainly. From the over-lay relationship between five kinds of vulnerable zones and current construction lands, about 53% of the construction lands distributed at zones with higher and middle vulnerability, and less than 10% distributed in zone with the lowest vulnerability. However, the distributions of three types of construction lands were different. Most of the urban & town lands were located in zones with the highest, higher and middle vulnerability, accounting for 29.63%, 36.65% and 21.90%, respectively. Moreover, minute quantity of urban & town land was located in zone with the lowest vulnerability. The distribution of rural settlements was more dispersed than urban & town land, and zone with the lowest vulnerability was of least proportion, which was about 12%. The other construction land was of similar spatial distribution pattern with rural settlements, but zone with the highest vulnerability was of least proportion, which was about 9%. As human factor has already caused the increasing of ecological vulnerability, future economic growth and regional development should turn to zones with lower and the lowest vulnerability. Based on zoning results, inducing factors, and the spatial relationship with current construction lands, suggestions on regional development or ecological protection were proposed accordingly.