The interactive effects of natural and human factors on ecosystems have been well studied, and the quantitative assessment of large-scale ecological vulnerability caused by natural and human factors is now one of the most active topics in the field. Taking the Guangxi Xijiang River Economic Belt in southwest China (GXEB) as a case study, we assess ecological vulnerability based on the Vulnerability Scoping Diagram (VSD) model. The indices system is decomposed into three sub objects, ten elements and 25 indicators layer by layer, which included factors from both natural and human fields. Results indicate that zones with lower, middle-lower, middle, middlehigher and higher vulnerability account for 11.31%, 22.63%, 27.60%, 24.39%, and 14.07%, respectively. The western and eastern parts of GXEB are more vulnerable than the central part and the mountain and urban areas are of higher vulnerability than the basins and river valleys. Compared with a vulnerability assessment based on natural factors only, it is concluded that human activities indeed cause the transition from naturally stable zones to vulnerable zones. The nature-dominated vulnerable zones are different with human-dominated ones in size and distribution, the latter being smaller, more scattered and distributed in urban areas and their surroundings. About 53% of total construction land is distributed in zones with middle and middle-higher ecological vulnerability; less vulnerable zones should attract construction in the future. Relevant suggestions are proposed on how to reduce vulnerability according to inducing factors. The VSD model has a significant advantage in the quantitative evaluation of ecological vulnerability, but is insufficient to distinguish nature- or human-dominated vulnerability quantitatively.