Response of the runoff in the headwater region of the Yellow River to climate change and its sensibility are analyzed based on the measured data at the four hydrological stations and ten weather stations during the period 1959-2008. The result indicates that change of temperature in the region has an obvious corresponding relationship with global warming and the changes of annual average temperature in each subregion in the region have been presenting a fluctuant and rising state in the past 50 years. However the change of precipitation is more intricate than the change of temperature in the region because of the influences of the different geographical positions and environments in various areas, and the change of annual precipitation in the main runoff-producing area has been presenting a fiuctuant and decreasing state in the past 50 years. And there is a remarkable nonlinear correlativity between runoff and precipitation and temperature in the region. The runoff in the region has been decreasing continuously since 1990 because the precipitation in the main runoff-producing area obviously decreases and the annual average temperature continuously rises. As a whole, the runoff in each subregion of the headwater region of the Yellow River is quite sensitive to precipitation change, while the runoff in the subregion above Jimai is more sensitive to temperature change than that in the others in the region, correspondingly.