Based on the panel data of 16 cities in Hubei Province from 2009 to 2019 (excluding the data during Covid-19 pandemic period), we construct multi-temporal difference-in-differences model (DID) and Spatial Durbin model (SDM) to explore the impact of the High-speed Railway (HSR) construction on the regional economic development in terms of direct economic effect, indirect economic effect and spatial spillover effect. The main conclusions of this paper are as follows: firstly, HSR construction promotes the economic development of cities in Hubei Province in a long time and in a large spatial scope. And the impacts on the economic development are significantly heterogeneous among different types of cities. Also, HSR construction has widened the economic development gap among cities to some extent. Secondly, the upgrading of an industrial structure and the improvement of urbanization level both play mediating roles in the economic impact of HSR construction. Thirdly, the HSR construction has significant spatial spillover effect on economic development, but the spillover effect becomes insignificant with the increase of distance.