Abstract: It is essential for basin water security and management to analyze the response relationship between runoff change and natural and human factors.We constructed a LSTM (Long Short-Term Memory) model with multiple factors as input and runoff as output to establish the response relationship between multiple influence factors including climate change and human activities and runoff.Then we analyzed the sensitivity and contribution rate between the multiple influence factors and runoff.We took the upper Huaihe River as a case study.The results show that the runoff sensitivity to human factors is higher than that to meteorological factors,and it has the highest sensitivity to reservoir capacity.The average sensitivity of all factors increased after mutation.The contribution rates of meteorological and human activities to runoff were 55% and 45% respectively.Changes in reservoir capacity,precipitation,and net radiation are the dominant factors in runoff reduction.Reasonable water conservancy project construction and ecological restoration layout will play a beneficial role in runoff regulation.The research results provide scientific reference and decision-making aid for the identification of runoff change rules and causes,the watershed underlying surface protection and water security.