Based on the data for meteorology, hydrology, soil, planting, vegetation, and socio-economic development of the irrigation region in the middle reaches of the Heihe River basin, Northwest China, the model of balance of water supply and demand in the region was established, and the security of water resource was assessed, from which the results that the effects of unified management of water resources in the Heihe River basin between Gansu Province and Inner Mongolia on regional hydrology are significant with a decrease in water supply diverted from Heihe River and an increase in groundwater extracted. In addition, it was found that the groundwater level has been steadily decreasing due to over pumping and decrease in recharges. In present year (2003), the volume of potential groundwater in the irrigation districts is far small because of the groundwater overdraft; even in the particular regions, there is no availability of groundwater resources for use. By 2003, water supply is not sufficient to meet the water demand in the different irrigation districts, the sustainable development and utilization of water resources are not secured, and the water supply crisis occurs in Pingchuan irrigation district. Achieving water security for the sustainable development of society, agriculture, economy, industry, and livelihoods while maintaining or improving the abilities of the management and planning of water resources, determining of the reasonable percentage between water supply and groundwater utilization and water saving in agricultural irrigation are taken into account. If this does not occur, it is feared that the present performance of water development and planning may further aggravate the problem of scarcities of water resources and further damage the fragile ecological system.