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The hydrological regime in arid and semi-arid regions is quite sensitive to climate and land cover changes (LCC). The Three-North region (TNR) in China experiences diverse climate conditions, from arid to humid zones. In this region, substantial LCC has occurred over the past decades due to ecological restoration programs and urban expansion. At a regional scale, the hydrological effects of LCC have been demonstrated to be less observable than the effects of climate change, but it is unclear whether or not the effects of LCC may be intensified by future climate conditions. In this study, we employed remote sensing datasets and a macro-scale hydrological modeling to identify the dependence of the future hydrological regime of the TNR on past LCC. The hydrological effects over the period from 2020-2099 were evaluated based on a Representative Concentration Pathway climate scenario. The results indicated that the forest area increased in the northwest (11,691 km(2)) and the north (69 km(2)) of China but declined in the northeast (30,042 km(2)) over the past three decades. Moreover, the urban area has expanded by 1.3% in the TNR. Under the future climate condition, the hydrological regime will be influenced significantly by LCC. Those changes from 1986 to 2015 may alter the future hydrological cycle mainly by promoting runoff (3.24 mm/year) and decreasing evapotranspiration (3.23 mm/year) over the whole region. The spatial distribution of the effects may be extremely uneven: the effects in humid areas would be stronger than those in other areas. Besides, with rising temperatures and precipitation from 2020 to 2099, the LCC may heighten the risk of dryland expansion and flooding more than climate change alone. Despite uncertainties in the datasets and methods, the regional-scale hydrological model provides new insights into the extended impacts of ecological restoration and urbanization on the hydrological regime of the TNR.