In order to analyze the contribution rate of runoff variability from climate change and human activities in the Nam Ngum River Basin in Laos since the 1960s, the daily precipitation data from two widely used satellite precipitation products in the Mekong River Basin, APHRODITE and MSWEP, were bias-corrected based on the measured precipitation data from ground stations in the basin. The Xin’anjiang model was constructed using corrected satellite daily precipitation and measured daily runoff data from Pakkanhoung and Hinheup stations during reference period, and the natural daily runoff process in the basin during reservoir influence periods was simulated. The contribution rate of climate change and human activities to runoff variability was quantified. The results show that there is a general downward trend in annual runoff in the Nam Ngum River Basin. The contribution rates of climate change to the runoff variability during the two reservoir influence periods were -429% and -399% at the Pakkanhoung station, respectively, and the contribution rate was -380% at the Hinheup station. The corresponding anthropogenic contribution rates were 529%, 499% and 480%, respectively. Anthropogenic activities are the main cause of runoff variability in the basin. Anthropogenic activities mainly based on reservoir operation, have a significant imp.