Objective:To explore the spatiotemporal distribution and macro-related factors of congenital syphilis in Guangdong province and provide suggestions and recommendations for prevention.Methods:Yearly reported cases of syphilis and some influencing factor data of Guangdong province were collected from 2005 to 2017. The spatiotemporal distribution of congenital syphilis was described. Meanwhile, the spatial panel data model was constructed to analyze the relationship between the incidence rates of congenital syphilis and related factors.Results:From 2005 to 2017, 13 361 cases of congenital syphilis were reported in Guangdong province. The number of congenital syphilis cases rose to its highest point during 2005-2011. A slow downward trend followed. The peaks of incidence were observed from August to December. The incidence of the non-Pearl River Delta region has experienced a process of rising first and then decreasing. The spatial panel data model results showed that congenital syphilis had significant positive spatial autocorrelation ( P<0.001). The incidence of primary and secondary syphilis in women ( β=0.822, P<0.001), gross domestic product per capita ( β=3.511, P<0.001), net migrate rate ( β=0.215, P=0.047) and maternal system management rate ?(β=0.017, P=0.021) were all positively correlated with the incidence rates of congenital syphilis. Registered population density ( β=-1.167, P<0.001) and prenatal examination rate ( β=-0.038, P=0.031) was negatively correlated with congenital syphilis. Conclusions:The incidence of congenital syphilis was spatially aggregated in Guangdong province from 2005 to 2017. The intensity of prevention might be strengthened in cities with developed economies and high net migration rates, which have high risks of congenital syphilis. Controlling the incidence of primary and secondary syphilis in women and increasing the prenatal examination rate for pregnant women appears effective prevention measures of congenital syphilis.