The variation trend and the abrupt changes of runoff in the Lhasa River Basin were analyzed, the contributions of climate change and human activities to runoff were quantitively calculated to provide statistical support for the management and utilization of water resources in the area. Based on the runoff and precipitation data from 1956 to 2016, the variation trend and abrupt changes of runoff were analyzed using Mann-Kendall trend analysis, cumulative anomaly-sliding t test method and double mass curve method, as well as the contribution of precipitation and human activities to the runoff change from June to September. The results showed that in the past 61 years, the inter annual variation of the runoff fluctuated greatly, and abrupt changes of flood season runoff occurred in 1995 and 2005. Using the years of 1956-1994 as the base period, the quantitative analysis of the double mass curve method revealed that the proportion of human activity contribution to the runoff from 1995 to 2004 was less than 50%, then it rose up to be more than 70% in the period of 2005-2016, which became the dominating influencing factor of runoff changes in flood season with a greater impact on the lower reaches of the river. This is mainly attributed to the newly built Zhikong Reservoir and Pangduo Reservoir, which regulated the flow process.