Ecological safety has faced serious threats from soil acidification, erosion and rocky desertification caused by natural disasters and increasing human activities in Guangxi. NPP which can effectively reflect productivity of plant community in the environment is one of the key indices for assessing the function of ecosystem service. The vegetation net primary productivity (NPP) in Guangxi province from 2000 to 2011 was estimated using the light use efficiency model and the time-series NDVI of MODIS data. And the spatio-temporal variation of vegetation NPP was analyzed based on several affecting factors, such as climate, vegetation types, soil types, topography, and human activities. The results showed that the NPP had increased in Guangxi province on the whole, especially the southwestern area. However, it decreased gently around Guilin and Liuzhou in recent 12 years. There was a significant positive relationship between total NPP and annual precipitation, while no significant relationship between total NPP and annual average temperature. The spatio-temporal variation characteristics of NPP changed with different vegetation types and soil types. The NPP of cultivated vegetation had been increased constantly and the human activities had become the important role on the NPP variation gradually.