In recent years, extreme weather events have happened frequently in the south of China, especially with the frequent occurrence of droughts. Vegetation is an important environmental factor, which is a comprehensive reflection of human activities and the natural environment. In this study, we selected the Pearl River Basin as a study area, using MODIS Enhanced Vegetation Index data, and analyzed the vegetation changes resulting from human activity and natural environment. Where human activities are present, our analysis mainly used DMSP data from the United States military meteorological satellite to analyze light data changes from 2004 to 2013. Natural environments were analyzed mainly by meteorological stations; the main parameters analyzed included mean daily temperature and precipitation. The results show that in the Pearl River Basin, the yearly average Enhanced Vegetation Index was between 0.33 to 0.38 during 2004 to 2013, the order of Enhanced Vegetation Index was as follows: evergreen broad-leaved forest > mixed forest > woody savannas > evergreen coniferous forest > grassland. In addition, during this period, the level of urbanization increased by approximately 71%, and the changes in urban development trends were opposite to those of Enhanced Vegetation Index. Thus, the results of this study showed that human activity is the major stress factor causing vegetation changes in the Pearl River Basin and that the natural environment is not dominant.