Due to the impact of climate change and human activities, the rainfall-runoff relationship in the Yellow River Basin has undergone significant changes, seriously affecting the planning and management of water resources in the basin. In order to reveal the change characteristics, trends and main driving factors of the rainfall-runoff relationship in the Yellow River Basin, we adopted Mann-Kendall test, double accumulation curve method, Copula function and slope change ratio of cumulative quantity (CSRCQ) method to analyze the spatio temporal variation of runoff coefficient, years with abrupt changes of rainfall-runoff relationship in seven main regions, probability change of rainfall-runoff combination, and the contribution rate of climate change and human activities to the relationship in the Yellow River Basin during 1960-2010. Results show that the changes of the rainfall-runoff relationship in the whole basin showed obvious trend characteristics, among which the runoff coefficient in most areas showed a downward trend, except that the source area of the Yellow River showed no obvious change and a few areas had a tendency to increase. The abrupt change years of the seven main regions of above Tangnaihai, Tangnaihai-Lanzhou, Lanzhou-Toudaoguai, Toudaoguai-Longmen, Longmen-Sanmenxia, Sanmenxia-Huayuankou and Huayuankou-Lijin were 1989, 1984, 1997, 1979, 1992, 1987 and 1970 respectively. The time difference of the abrupt changes was mainly affected by the time of human activities. Moreover, the year when large scale soil and water conservation measures were carried out in the basin and the time when water conservancy projects were constructed were all important factors that caused the turning point of the relationship between rainfall and runoff. After the abrupt change of the rainfall-runoff relationship in the main regions of the Yellow River Basin, the runoff generation capacity under the same rainfall conditions decreased. Human activities were the main driving factors for changes of the relationship between rainfall and runoff, with a contribution rate of more than 50%, and the further downstream, the greater the impact.