The rainfall-runoff relationship in Sanchuan watershed has changed significantly due to the climate change and intensive human activities. The variation of rainfall-runoff relationship threatens the urban water supply and spring protection work in Jinan city. In this paper, we investigated the variation patterns and analyzed the internal mechanism and driving factors that caused the variation of rainfall-runoff relationship in the past fifty years (1964-2011). The Mann-Kendall test,cumulative anomaly, and sliding partial correlation coefficient methods were used for characteristics analysis. The analysis results indicated that the rainfall increased significantly due to the climate change. However, the runoff decreased insignificantly in the past fifty years due to human activities such as soil and water conservation and water consumption for social and economic purposes. The change-point of rainfall-runoff relationship occurred in 1988. The annual rainfall in 1988-2011 increased by 12.57% and the annual runoff decreased by 8.85% as compared to those prior to the change-point (in 1964-1987). The human activities including water storage and supply projects and soil and water conservation practices were the main factors impacting the rainfall-runoff relationship in Sanchuan watershed. The analysis demonstrated that the climate change and human activities had opposite effects on the rainfall-runoff relationship in Sanchuan watershed.