Abstract：Based on the opening data of China’s high?speed railway from 2006 to 2016，the opening of high?speed railway is considered a natural experiment scenario，and the approach of using the multi?time point differential method to empirically test the impact of high?speed railway opening on the rationalization and upgrading of urban industrial structure is developed. It is found that the opening of high?speed railway promotes the advanced industrial structure of municipal districts，aggravates the irrational industrial structure， and promotes the transfer of the proportion of the secondary industry to the tertiary industry in county?level cities，and this effect does not start from the construction period. Through further research，it’s found that opened high?speed municipal districts by reducing the number of industrial enterprises above designated size by high?level industrial structure，municipal district is located in the urban cluster enhances the high?speed opened effects on the industrial structure is unreasonable，while promoting county is located in the urban cluster by high?level opened high?speed urban industrial structure.