Based on RS and GIS technology, the grassland cover spatio-temporal variation of Qilian Mountains was analyzed using cumulative average method, average method, trend line analysis, image differencing with the SPOT VGT-NDVI data, and Hurst exponents were utilized to predict the future trends of grassland cover change in Qilian Mountains. The results show that: (1) the grassland vegetation NDVI has been in creused in Qilian Mountains from 1999 to 2007. The increase rate of annual average NDVI and growing season NDVI in typical steppe and plain grasslands was higher than that in alpine meadow and desert grasslands. The increased and reduced areas were 69776 km2 and 15928 km2, respectively. The grassland vegetation NDVI in Lenglong Ridge, Laji Mt., Datong Mt., Daban Mt., South Qinghai Mt., Zongwulong Mt., Tuolai Mt., South Tuolai Mt. was improved, and comparatively, the grassland vegetation NDVI was reduced in Wushao Ridge, the valleys of Datong River, Shiyang River, Heihe River, Beida River and Shule River and the surrounding areas of Qinghai Lake. (2) The grassland vegetation NDVI of Qilian Mountains with a single peak curve during the year changer in Qilian Mountains. (3) The grassland cover in Lenglong Ridge, Zongwulong Mt., South Qinghai Mt., Jingtie Mt., Laji Mt., Wushao Ridge; the valley of Datong River, Hei River, Beida River, Shule River and the surrounding areas of Qinghai Lake will be sustainably improved in the future, and the grassland cover will be degraded in South Zoulang Mt., Tuolai Mt., South Tuolai Mt., Datong Mt. and the valleys of Huangshui and Shiyang rivers. The cover of desert grasslands and alpine meadow grasslands will be improved, and the typical steppe and plain grasslands will be degraded in the future.