Guizhou Province is an important karst area in the world and a fragile ecological area in China. Ecological risk assessment is very necessary to be conducted in this region. This study investigates different characteristics of the spatial-temporal changes of vegetation cover in Guizhou Province of Southern China using the data set of SPOT VEGETATION (1999-2015) at spatial resolution of 1-km and temporal resolution of 10-day. The coefficient of variation, the Theil-Sen median trend analysis, and the Mann-Kendall test are used to investigate the spatial-temporal change of vegetation cover and its future trend. Results show that: 1) the spatial distribution pattern of vegetation cover in Guizhou Plateau is high in the east whereas low in the west. The average annual normalized difference vegetation index (NDVI) from west to east is higher than that from south to north. 2) Average annual NDVI improved obviously in the past 17 years. The growth rate of average annual NDVI is 0.028/10 yr, which is slower than that of vegetation in the country (0.048/10 yr) from 1998 to 2007. Average annual NDVI in karst area is lower than that in non-karst area. However, the growing rate of average annual NDVI in karst area (0.030/10 yr) is faster than that in non-karst area (0.023/10 yr), indicating that vegetation coverage increases more rapidly in karst area. 3) Vegetation coverage in the study area is stable overall, but fluctuates in the local scales. 4) Vegetation coverage presents a continuous increasing trend. The Hurst exponent of NDVI in different vegetation types has an obvious threshold in various elevations. 5) The proportion of vegetation cover with sustainable increase is higher than that of vegetation cover with sustainable decrease. The improvement in vegetation cover may expand to most parts of the study area