The terrestrial water cycle is influenced by a wide range of climatic variables and human disturbances. In the era of the Anthropocene, when humans drive the changes in atmospheric and hydrological processes in river basins, there is an urgent need to include human impacts in the study of the terrestrial water cycle. This paper focused on the large-scale hydrological modeling which takes account of human impacts, reviewed the research progress of the natural and human-induced changes in the terrestrial water cycle and the development of comprehensive terrestrial hydrological models in recent years, and proposed that an integrated water system model with human-related processes such as crop water demand model, engineering regulation and social water demand, be the key to large-scale water cycle simulations under changing environment. Based on the existing large-scale land surface hydrological model, there is a need to put forward the integration of the human-related processes. A comprehensive integrated water system model that considers multi-processes can help us to understand the key mechanisms of how climate change and human activity influence the regional water cycle. It also provides a theoretical and practical basis for investigating the causes and effects of changes in terrestrial water cycle under a changing environment, and thus offers scientific support for climate change adaptation in the water sector.