From the perspective of improving input-output efficiency, this paper builds a theoretical framework for the impact of high-speed rail on the high-quality development of cities in ethnic minority areas. Based on the high-speed rail operation and economic and social development data of prefecture-level cities in eight ethnic provinces from 2006 to 2017, this paper empirically tests the overall impact of high-speed rail on the high-quality development of cities in ethnic minority areas and its sources, and investigates the possible impact mechanism. The results show that from the perspective of the overall impact and its sources, high-speed rail has a positive impact on the high-quality development of cities in minority areas, and the impact is mainly due to the promotion of technological innovation and economies of scale; from the perspective of heterogeneity and dynamics, the impact of high-speed rail on high-quality urban development in ethnic areas varies with the basis of urban development, and the positive effect has a time lag of about three years. From the perspective of influence mechanism, high-speed rail will exert different influences on the high-quality development of cities in ethnic minority areas through three mechanisms: investment promotion of fixed asset investment, industrial driving of tourism industry development and output driving of green development. In the future, it is necessary to further strengthen the construction of high-speed railway in ethnic minority areas, make up for the deficiencies of funds and factors of high-speed railway cities in a targeted way, and adopt differentiated development incentive policies for different cities, so as to promote the high-quality development of cities in ethnic minority areas by taking advantage of high-speed railway.