This study retrospectively analyzed the spatio-temporal distribution and spatial clustering of scarlet fever in mainland China from 2004 to 2017. In recent years, the incidence of scarlet fever is increasing. Previous studies on the spatial distribution of scarlet fever in China are mainly focused at the provincial and municipal levels, and there is few systematic report on the spatial and temporal distribution characteristics of scarlet fever on the national level. Based on the incidence information of scarlet fever in mainland China between 2004 and 2017 collected from the China Center for Disease Control, this paper systematically explored the Spatio-temporal distribution of scarlet fever by three methods, contains spatial autocorrelation analysis, Spatio-temporal scanning analysis, and trend surface analysis. The results demonstrate that the incidence of scarlet fever varies by seasons, which is in line with double-peak distribution.The first peak generally occurs from May to June and the second one from November to December, while February and August is the lowest period of incidence. Trend surface analysis indicates that the incidence of scarlet fever in northern China is higher than the south, slightly higher in western compared to the east, and lower in the central part. Additionally, the results show that the clustering regions of scarlet fever centrally distributed in the northeast, northwest, north china and some provinces in the east, such as Zhejiang, Shanghai, Shandong, and Jiangsu.