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This study is to empirically investigate the impact of urbanization through improving transportation infrastructure, reflected by introducing high-speed rail (HSR), on the regional development with the interaction of the socioeconomic factors reflected by industrial structure. An advanced quantitative tool named multi-period difference-in-differences (DID) method is applied. We find the impact of urbanization through HSR on regional development is mixed while interacting with industrial structure helps to explain heterogeneities of the impact. The more the industrial structure tends to be agricultural, the greater the negative impact of HSR opening on regional economic development; meanwhile, the more the industrial structure evolves to be service-oriented, the greater the positive impact of HSR. This study highlights the importance of the interaction between urban growth and socioeconomic factors, which would provides a reference for government and urban planners to make decisions on introducing HSR or improving transportation infrastructure.