Cultural relics protection units are important carriers of Chinese outstanding traditional culture. It is of great significance to study the spatial differentiation of cultural relics protection units and the differences in the results of multi-scale driving factors, in order to continuously promote the inheritance of history and culture, and to prosper the development of regional cultural undertakings and cultural industries. Huizhou cultural relics protection units were taken as the research object, and standard deviation ellipse, kernel density estimation and geographic detector methods were used in the analysis of spatial and temporal differentiation and driving factors of cultural relics protection units. The results show that the cultural heritage units in Huizhou region present the time series characteristics of "dispersed-concentrated-dispersed", and the center of distribution gradually shifts from the middle to the south. The spatial aggregation of cultural heritage units is remarkable, the overall performance of the "V" distribution pattern, specifically concentrated in Shexian County and Jixi County. Natural geographic factors and human geographic factors have an impact on the spatial differentiation of cultural heritage units.