The rapid development of the high-speed rail (HSR) network enhanced the regional accessibility between cities, drove the rise in cities’ investment levels, and expanded the activity radius of the labor force, causing changes in housing prices along the rail lines. Based on panel data of 285 cities in China from 2008–2016, this study used the difference-in-difference based on propensity score matching (PSM-DID) method to calculate the impact of HSR on housing prices. The conclusions of the study indicated that, at the regional level, HSR significantly promoted the rise in housing prices in HSR cities along the rail line. HSR had a positive effect on housing prices, where the coefficient of HSR influence was 0.1511 and passed a 1% significance test. From the perspective of the combination of sub-regional and sub-city scales, HSR mainly played a significant role in promoting housing prices in “small and medium-sized cities” and “central and western cities”, especially in small and medium-sized cities in the central and western regions; in general, HSR can narrow the housing price gap between “small and medium-sized HSR cities” in the central and western regions and large HSR cities in the east region. Lastly, the results of the intermediary mechanism test showed that the income level of residents and employment levels played an intermediary role in the influence of HSR on the housing prices of cities along the rail line. Thus, this paper suggests that the Chinese government needs to formulate housing price control policies that suit local conditions according to the characteristics of different cities.