Since the Medium and Long-term Railway Network Plan was promulgated, high-speed railway construction in China entered a stage of large-scale development and China gradually ushered in the age of high-speed railway. As urbanization sped up, the railway exerted major influence over the development of cities and areas along the line. The paper takes remote sensing images of cities along the Beijing-Shanghai High-speed Railway as basis and resorts to GIS technology and multiple research methods to comparatively analyze and measure the impact of this particular railway on spatial expansion of cities along the line from 2005 to2014. Result of the research indicates that from 2005 to 2014, size of built-up areas in cities along the Beijing-Shanghai Highspeed Railway expanded by 54.28%, and overall expansion speed and intensity of the cities along the Beijing-Shanghai Highspeed Railway were both 6.78%, which signaled that the railway promoted the spatial expansion of the cities. The southern cities, such as Shanghai, Changzhou, Suzhou in Jiangsu, become the hot areas of the spatial expansion. And the spatial expansion of the cities differed in speed and intensity and the direction of expansion showed anisotropy.