Abstract: The opening of high-speed railways has made a significant difference in the construction of cities along the railway. Based on accessibility measurement and modified economic potential model, an in-depth analysis of the accessibility and economic potential of high-speed railways in AnhuiProvince was conducted through using GIS. The research results are shown as follows: ①After the opening of high-speed railways, the accessibility of Anhui province significantly improved, but the overall pattern remained unchanged, which took on a “multi-core” mode centering on Hefei and taking Huainan and Wuhu as sub-centers. The accessibility of Chizhou and Tongling improved to the largest degree, followed by Huangshan; the change of Wuhu and Chuzhou in accessibility was the smallest. After the opening of high-speed railways, the accessibility of Chuzhou decreased to the largestdegree, ranking the fifth; Hefei, Huainan and Huangshan were the most stable cities; other cities changed slightly.②The improvement of accessibility had a certain effect on the economic potential of the city; generally, a peripheral expansion mode centering on Hehui was presented. The economic potential growth in Chizhou and Tongling was the most significant; Huangshan ranked the third. Obviously, the improvement in accessibility had a direct impact on the economic development of Chizhou, Tongling, and Huangshan. After the opening of high-speed railways, Hefei and Wuhu ranked the second in terms of economic potential, and their status as traditional economic center didn’t change. The economic potential in Ma’anshan increased to the largest degree, ranking the fourth. But for Chizhou and Huangshan, their economic potential was still relatively weak, ranking last. ③After the opening of high-speed railways, the time-space astringency effect was significant. The improvement of accessibility dramatically promoted the growth of economic potential, but affected by many factors, the relationship between accessibility and economic potential was not fully harmonious.