As an important part of the National Natural Science Foundation, the Regional Science Fund has made positive contributions to local social and economic development since its establishment. The analysis of the input and output of Regional Science Fund through scientific method is helpful to improve its efficiency and management level. Based on this, the paper proposes an input-output efficiency evaluation method combining information entropy and DEA model, and sets up an evaluation system for input and output efficiency of Regional Science Fund and analyzes the data of the regional science fund that was completed in Jiangxi province from 2005 to 2014. The results shows that the overall input-output efficiency of science funds in Jiangxi province is higher than the national average, but the scale efficiency needs to be strengthened, the annual efficiency is not stable and greater gap in efficiency values was existed among disciplines. To this end, it is proposed that Jiangxi province should adjust the scale of investment appropriately and formulate a favorable research policy based on the comprehensive consideration of the inherent characteristics of various disciplines so as to improve the total efficiency of fund input.