Abstract: This paper describes a crop planting structure optimization model based on the concept of water footprint. The water footprint theory is used to evaluate blue and green water footprints of regional main crops and then a fractional programming model is developed for maximizing the efficiency of agricultural water resource utilization by various crops with differences in crop features, spatial distribution, and water footprint. The model is applied to a real case of the Yangtze River-Yellow River-Lancang River headwaters area in Qinghai Province, and the crop planting structure is optimized by high profit and less irrigation water use for satisfying the local food demand. Compared with the current situation, the optimized structure suggests a significant increase in the planting area of vegetables with the highest profit and lowest water consumption and a slight increase in that of pea and potato with high profit and low water consumption, while maintaining the existing planting scale of crops with low profit and high water consumption such as wheat, highland barley and rapeseed. Results could be helpful for improving water utilization and providing basis on water management in the study area and other relevant areas.