To explore the relationship between vegetation cover change and climatic changes, we used MODIS NDVI (2000-2016) data set and climate (temperature and precipitation) data to analyze temporal and spatial variation characteristics of vegetation cover and its correlation with climatic factors in the Hotan Prefecture from 2000 to 2016. The results showed the following:(1) The data for inter-monthly changes in vegetation cover in the Hotan Prefecture during the last 17 years showed that vegetation cover first increased and then decreased. The inter-annual variation showed a significant upward trend, with a growth rate of 0.452/10a; (2) In the past 17 years, the areas where vegetation cover increased and decreased accounted for 4.48% and 0.21% of the total area, respectively. The oasis and the northern part of the Kunlun Mountains changed considerably, and the high-altitude area remained basically unchanged; (3) Over the past 17 years, temperature and precipitation increased slightly, with growth rates of 0.144/10a and 0.156/10a, respectively. On a monthly scale, vegetation cover was positively correlated with temperature, and vegetation growth lagged behind temperature for two months. There was a negative correlation with precipitation, but the lag effect was not obvious. (4) In the spatial distribution of NDVI response to climate factors, NDVI was negatively correlated with average temperature and positively correlated with precipitation. The correlation with precipitation was higher than that with temperature. Therefore, we conclude that vegetation in the northern Kunlun Mountains is more sensitive to precipitation changes, and the oasis and mountains in southwestern Hotan Prefecture are more sensitive to temperature changes.