Mountainous runoff is very important to the inland river basin in Northwest China, because it is related to the oasis ecological environment security and the social and economic sustainable development in the middle and lower reaches of the basin. Therefore, more and more studies are focused on the changes of mountainous runoff under the climate change in this region. The Shule River is one of the three largest inland river in Hexi Corridor, Gansu Province, Northwest China. Based on the runoff data at Changmabu hydrological station and the meteorological data of the Shule River Basin during the period 1958-2015, this article analyzed the characteristics of mountainous runoff of the Shule River Basin and its response to the climate change. The trend of mountainous runoff is analyzed by the line trend method. The mutation of mountainous runoff is analyzed by the Cumulative departure method. Morerover, the evapotranspiration is calculated by the Takahashi formula, and the relationships between mountainous runoff and climate factors are analyzed by the Correlation and Sliding correlation method. The main results were obtained as follows: In general, the mountainous runoff of the Shule River Basin presents an increasing trend in the research periods, and this trend was more obvious since the late 1990s, however, it is declined slowly in recent years. Moreover, the runoff series appears an obvious mutation in 1997. Finally, the correlation analysis shows that precipitation was the main control factor for the mountainous runoff changes. At the same time, the increased snow and ice melt caused by the rising temperature was the main reason for the changes of mountainous run off in recent years. In a word, the variability of runoff depends on the comprehensive impact of the climate factors for the effect of each factor is inconsistent in different stage.