Based on the precipitation and temperature data of the 12 meteorological stations in the “Three-River Headwaters” region and the observed runoff data of Zhimenda in the headwater sub-region of the Yangtze River, Tangnaihai in the headwater sub-region of the Yellow River and Changdu in the headwater sub-region of the Lancang River during the period 1965-2004, this paper analyses the trends of precipitation, temperature, runoff depth and carries out significance tests by means of Mann-Kendall-Sneyers sequential trend test. Makkink model is applied to calculate the potential evaporation. The runoff model driven by precipitation and potential evaporation is developed and the influence on runoff by climate change is simulated under different scenarios. Results show that during the period 1965-2004 the temperature of the “Three-River Headwaters” region is increasing, the runoff of the three hydrological stations is decreasing and both of them had abrupt changes in 1994, while no significant trend changes happen to the precipitation. The runoff model suggests that the precipitation has a positive effect on the runoff depth, while the potential evaporation plays a negative role. The influence of the potential evaporation on the runoff depth of the Lancang River is found to be the significant in the three rivers; and that of the Yellow River is the least. The result of the scenarios analysis indicates that although the precipitation and the potential evaporation have positive and negative effects on runoff relatively, fluctuated characteristics of individual effect on the runoff depth in specific situations are represented. Based on the precipitation and temperature data of the 12 meteorological stations in the “Three-River Headwaters” region and the observed runoff data of Zhimenda in the headwater sub-region of the Yangtze River, Tangnaihai in the headwater sub-region of the Yellow River and Changdu in the headwater sub-region of the Lancang River during the period 1965-2004, this paper analyzes the trends of precipitation, temperature, runoff depth and carries out significance tests by means of Mann-Kendall-Sneyers sequential trend test. The runoff model driven by precipitation and potential evaporation is developed and the influence on runoff by climate change is simulated under different scenarios. Results show that during the period 1965-2004 the temperature of the “ Three-River Headwaters ”region is increasing, the runoff of the three hydrological stations is decreasing and both of them had abrupt changes in 1994, while no significant The runoff model suggests that the precipitation has a positive effect on the runoff depth, while the potential evaporation plays a negative role. The influence of the potential evaporation on the runoff depth of the Lancang River is found to be the significant in the three rivers; and that of the Yellow River is the least. The result of the scenarios analysis that that though the precipitation and the potential evaporation have positive and negative effects on runoff relatively, fluctuated characteristics of individual effect on the runoff depth in specific situations are represented.