The spatial interaction of urban system has been an hot research issue in the field of urban research. In this paper, user’s microblog spatial information data were used to discern the spatial structure of an urban area. Firstly, Sina Weibo microblog data for 2011–2015 were used to establish a thematic database of cities along the Huaihe River Basin, China. Secondly, network connectivity, inflow, and outflow of three indicator systems were analyzed. Finally, combining this database with socioeconomic data, experimental verification and comparative analysis were carried out. The study found that the urban spatial relation in the Huaihe River Basin has the following characteristics: the spatial difference of urban size distribution is obvious; urban layout presents a stratified aggregation phenomenon; and the high-grade cities lead the city’s interaction. The research shows that this method of data mining for urban interaction in the Huaihe River Basin is valid and that this research into urban spatial patterns of river basins is applicable to other areas.