Studying the variation characteristics of meteorological and hydrological factors and attribution of runoff variation in the Qinhuai River Basin has important guiding significance for the prevention of flood and drought disasters in the basin. Based on the meteorological and hydrological observation data and remote sensing data, the β-z-h three parameters comprehensive indicator method was used to study the spatiotemporal variation trend of meteorological and hydrological elements, and joint mutation detection method was used to determine the variation points and variability of meteorological and hydrological elements. The elasticity coefficient method based on Budyko hypothesis was used to quantitatively evaluate the contribution rate of climate change and human activities to runoff change. The results showed that: (1) The annual average temperature and annual runoff depth in the Qinhuai River Basin show a significant increasing trend and will continue to increase in the future; the annual precipitation and reference crop evapotranspiration did not increase significantly and will continue to increase slightly in the future; but the annual average relative humidity showed a significant downward trend, and the significant downward trend will continue in the future. The precipitation did not have a alteration, the annual average temperature had a strong alteration in 1994, the annual average relative humidity had a giant alteration in 2004, the reference crop evapotranspiration had a moderate alteration in 2003, and the runoff depth had a weak alteration in 2002. (2) There was a significant positive correlation between runoff depth and precipitation in the base period (1981-2002) and change period (2003-2019), and there was a negative correction between runoff depth and reference crop evapotranspiration, underlying surface index. During the change period, the elasticity coefficient of reference crop evapotranspiration and underlying surface index increased, while the elasticity coefficient of precipitation decreased. The main factor contributing to the increase of runoff was the underlying surface index (91.20%) change, which indicated that the change of underlying surface caused by human activities was the main factor of runoff increase and played a positive role in the increase of runoff. In the process of urban development, the hydrological effects of land use and cover change should be fully considered, farmland and woodland with strong detention capacity should be protected, moreover, the flood control pressure brought by climate change should be paid attention to.