With the combination of field survey and EPIC modeling, this paper simulated the restoration effect of soil moisture in different alfalfa (Medicago sativa)-grain rotation systems in semi-arid and drought-prone regions of Loess Plateau. In perennial alfalfa field and in grain crop field after alfalfa, the correlation coefficients between the simulated and observed values of soil moisture content in 0-10 m layer were larger than 0.9 (P < 0.01), and their relative root mean square errors were between 0.05 and 0.16, with the relative errors less than 10%. The dynamic changes of the simulated soil moisture contents in different soil layers were consistent with those of the observed values. In the study regions, it was difficult for the restoration of soil moisture in the deep soil layers of alfalfa field. During the cultivation of alfalfa, the soil moisture content in the layers at 8-10 m depth should not be less than 5.7%. Considering the sustainable development of agricultural production, the appropriate cultivation duration of alfalfa should be 4-6 years and no more than 8 years. For the restoration of soil moisture after alfalfa cultivation in the study regions, the rotation system potato (Solanum tuberosum) --> potato --> spring wheat (Triticum aestivum) could be adopted, and alfalfa could be cultivated again after 32-33 years.