In the post-COVID-19 period, the regional economic development gap in Guangdong has expanded and the risk has increased. This is not conducive to building a well-off society in Guangdong in an all-round way. Optimizing the industrial structure, changing the mode of economic growth, preventing regional economic risks, and narrowing the regional economic development gap are the focus of Guangdong governments at all levels. Based on a two-sector economic growth model, the paper uses descriptive statistics and Deng's grey correlation method to analyze the economic development panel data of 21 prefecture-level cities of Guangdong Province from 2011 to 2018, analyzes the characteristics of regional economic development in Guangdong, and makes experimental research of the effect of industrial structure optimization and economic development factors on economic growth in Guangzhou, Zhongshan, Shantou, Maoming and Meizhou at different stages of development. The results show that: there are differences in the industrial structure and the level of economic development in different regions; the rationalization of industrial structure and upgrading of the industrial structure has an impact on economic growth and show different features during different stages; in different stages of economic development, foreign trade, scientific and technological innovation are the main factors affecting regional economic growth. This paper holds that the northwest of Guangdong Province and the Pearl River Delta should formulate industrial structure adjustment policies to promote the rationalization of regional industrial structure, expand foreign trade channels and innovate financing mechanisms, and restrain regional economic risks in combination with regional characteristics. The new development pattern of domestic and international dual circulation and mutual promotion, further expands the level of opening up, effectively playing the role of free trade pilot areas, free trade ports, special economic zones, development zones, bonded areas, and other frontier highlands, improve the level and capacity of foreign trade.