Abstract: China's food production and food security relates not only to the social stability and national security, it also affects the world food security situation. After the founding of New China, China's grain production has made remarkable achievements to solve the food problem of the 22% of the population, with 7% of the world's arable land. But as China's population growth and per capita cultivated land decreases continuously, the need to protect the national security of food production and to maintain social stability, received the wide attention of numerous experts and scholars. Since 1952, China's total grain output increased, which can be completely attributed to the grain yield increase. Grain yield levels and its fluctuation directly influence food production and its stability. In the hilly region of the Huaihe and Yangtze River, the average year's food production for 12-14 million t, accounting for about 45% of the total grain output in Anhui province, is one of the main producing areas of grain and oil in Anhui province. But due to particular climatic conditions, geographical location, geographical characteristics and the impact of human activity, frequent drought disasters occur in history. In particular, in the dry-zone in Hilly region of Huaihe and Yangtze River, due to higher terrain, backbone River less, and far away from the rivers, lakes and reservoirs, no lead water conditions, irrigation guarantee rate lower, the suffering drought disasters, and the existence of a large number of easy to dry land, it is one of the most arid regions of Anhui province. Through integrated management of cultivated land in drought-prone areas, raising the level of grain yield per unit area is the important strategic task and the main way to guarantee the safety of grain production in the hilly region of the Huaihe and Yangtze Rivers. Therefore, how to fully exert the cultivated land potential yield and stable increase grain yield, appear particularly important. Based on this, application of empirical mode decomposition (EMD) for grain yield and influencing factors of multi-level, multi-time scale decomposition, and reasonable use of set pair analysis (SPA) theory were used to analyze correlations between fluctuations in grain yield per hectare components and corresponding impact factors. Then the data was used to formulate a quantitative analysis of the influence factors on comprehensive effect rates of fluctuation of grain yield per hectare. On this basis, through the analysis of the impact drought and natural disaster on grain production of hazard degree, the data was used calculate the comprehensive effect rates of drought on fluctuations of grain yield per hectare. The analysis results of the series models in easy arid regions of the Huaihe and Yangtze River watershed shows that the series models has been a good combination of EMD and SPA theory, achieved on grain yield per hectare fluctuation at different time scales and quantitative multi-factor analysis, to find out the comprehensive effect rates of drought on fluctuations of grain per unit yield in easy arid regions of the Huaihe and Yangtze River watershed. It can provide a scientific basis for the comprehensive management of drought and food production decision-making in the hilly region of the Huaihe and Yangtze River, and has a certain value of popularization and application.