Transportation infrastructure is an important factor driving regional economic growth, and scientifically evaluating the economic growth effects of key transportation infrastructure is an important theoretical issue of development economics. This paper takes the opening of Dongguan Humen Bridge as a quasi-natural experiment, and quantitatively identifies the regional growth effect it brings. This paper uses panel data from 21 prefecture-level cities in Guangdong Province from 1991 to 2007, and based on the synthetic control method, assigns different weights to the cities in the control group to construct the “counterfactual” state of Dongguan where the Humen Bridge is not opened, so as to compare the difference in economic development between “real Dongguan City” and “Synthetic Dongguan City”. The results show that the opening of the Humen Bridge in 1997 made Dongguan’s GDP and GDP per capita exceed the theoretical level that could be achieved when the Humen Bridge was not opened. The opening of the Humen Bridge significantly changed the economic growth trend of Dongguan. With the passage of time, the opening of the Humen Bridge has continuously strengthened the promotion of Dongguan’s economic growth, indicating that the transportation infrastructure has a long-term effect on the promotion of regional economic growth. This work advances the research on the relationship between transportation infrastructure and regional economic growth.