Land use and landscape change are the core issues of global change research. Manas River Basin is a typical mountain-oasis-desert ecosystem in the arid areas. Based on the 3S technology and using the method of quantitative analysis the characteristics of landscape differentiation and its hydro-ecological effect in Manas River Basin were examined. The results showed that: (1) the artificialization and intensive trend of land use were obvious, ecological landscape continued to weaken; (2) land use changes presented the regional differences due to the special mountain-oasis-desert ecosystem, land use tended to highly altitude artificialization and structure stability in oasis area, then tended to highly sensitive and fragile ecology in periphery of oasis; (3) in mountain areas,oasis areas and desert areas, the characteristics of landscape differentiation was different ,the development of foreland pluvial fan led to the increase of landscape diversity in mountain areas; the distribution of patch became more nearby and tended to simplification and normalized in oasis areas; landscape pattern change was more complicated in desert areas, giving that the priority of the dominance and dominance index of water area decreased,the fragmentation of unused land increased; (4) the landscape change disrupted the hydrologic cycle in the upper reaches of Manas River, weakened the water resources allocation in the lower reaches of Manas River.