Rocky desertification is one of the most severe ecological issues that restrict the sustainable development of karst area in southwestern China. Compared with other ecosystems, mountain ecosystem is more sensitive to climate change due to its complex topography. Understanding the variation of vegetation growth associated to topographic factors is critical to promote ecological management in karst mountainous areas. Based on the Moderate Resolution Imaging Spectroradiometer Normalized Difference Vegetation Index (MODIS NDVI) data from 2000 to 2016, the spatial-temporal variation of NDVI in the karst mountainous area of Guizhou and Guangxi was analyzed. The topographical factors, including altitude, slope gradient, aspect and relief amplitude were introduced to examine the response of vegetation variation to topographical factors. The results showed that NDVI in the middle of karst mountainous area was higher than that in the northwest and southeast. Averaged NDVI during growing season showed a single-peak curve distribution with altitude, with the largest value (0.67) at an elevation of 400-600 m. However, no significant difference was found along the slope and aspect gradient. A greening trend occurred in the karst mountainous area, with an averaged increasing rate of 0.0018 yr-1, illustrating that the vegetation restoration in recent years tended to be better. More than 75% of the study area showed an increasing trend of NDVI, and about 20% of the study area, distributed in the western and southeastern parts of the region (southwest Guizhou and central Guangxi), performed a significant increase. Pixels with a decreasing trend of NDVI were only observed in the northeast and middle-eastern parts. The percentage of pixels with a significant increasing trend increased with the elevation gradient. The increased rate is higher at high altitude than that at low altitude, indicating that the ecological construction of vegetation at low altitude with gentle slope should be strengthened. These conclusions provide a scientific basis for the comprehensive treatment of rocky desertification and improvement of fragile ecological environment in the karst mountainous area in a certain sense.