Objective To analyze the spatiotemporal distribution characteristics of the syphilis epidemic in Gansu Province from 2005 to 2021, and to provide a reference for the prevention and control of the syphilis epidemic in Gansu Province. Methods ArcGIS 10.7 was used to map the annual incidence of syphilis in Gansu Province from 2005 to 2021, spatial autocorrelation analysis and local autocorrelation analysis were performed, and SaTScan 10.0.2 software was used for spatiotemporal scanning analysis. Results The global autocorrelation results showed that the annual incidence of syphilis in 2005-2021 was >0, Z＞1.96, and the P< 0.0001, showing a spatial clustering distribution, and the local autocorrelation results showed that there was one spatially similar high-high aggregation area and two spatially similar low-low aggregation areas in Gansu Province, and the hot spot analysis showed that there were 9 negative hotspot areas and 2 positive hotspot areas in the syphilis epidemic in Gansu Province. Spatiotemporal scanning analysis detected two high concentration areas, mainly concentrated in Gannan Tibetan Autonomous Prefecture. Conclusion Syphilis in Gansu Province has regional differences in space, and high-high accumulation areas in Gannan Tibetan Autonomous Prefecture persist, and targeted prevention and control strategies should be specified according to temporal and spatial characteristics.