Abstract: With the rapid improvement of urbanization, large cities have gradually formed a polycentric spatial structure through epitaxial expansion and connotative development. Under the effect of polycentric spatial structure, urban space, especially the change of housing price space, shows heterogeneity and complexity. Taking the fast-developing Hefei City as an example, this paper uses the geostatistical method to study the spatial differentiation characteristics of urban housing prices from different spatial scales, and analyzes the dominant factors of housing price differentiation by constructing the hedonic price model, to reveal the logical relationship between urban spatial structure and housing price space. The results show that: (1) On the scale of the main city, the spatial distribution of housing price is consistent with the polycentric structure, and three high housing price zones are formed in each center; (2) On the scale of central areas, the housing prices in each central area present a mixed distribution of circle layers and and fan-shaped. The difference in the impact scope of centers of different scales on their surrounding housing prices has formed different spatial variation patterns; (3) Among the three types of characteristics that influence the spatial differentiation of house prices, the structural and neighborhood characteristics have great influence on the main city, and scarce landscapes, educational resources and greening rate are the most important factors for spatial differentiation of housing prices in the main city; (4) The main factors of the spatial differentiation of house price in different central areas are various. The location characteristics have the greatest impact on the old city center, and the structural characteristics and location characteristics have a large impact in administrative center. Besides, the structural characteristics are the most important factors affecting housing prices in the center of the new district.