Abstract: Topographic relief can be the main constraining factor for the population and economic development in an area, and also the main index to evaluate the suitability of human settlement and the carrying capacity of natural resources. Based on the optimal statistical unit as determined by the mean turning-point analysis method, a DEM of 200 m resolution was used to extract the relief degree of land surface(RDLS) of Guangdong Province. Using the land use/cover data, the spatial modeling of population and economy was carried out to generate population and economic density maps. Then, by means of multi-data correlation analysis method, the spatial distribution rules of topographic relief, population and economic density were systematically analyzed. Finally, the spatial relationship between topographic relief and population and economy in Guangdong Province is deeply discussed. The results showed that: (1) The overall spatial pattern of the relief degree of land surface (RDLS) in Guangdong Province is strongly positively correlated with the elevation and slope, and is generally high in the north and low in the south, higher in the east and lower in the west, the RDLS area proportion shows a strong topographic gradient effect. (2) The natural discontinuities were used to divide the sparse population areas and the dense population areas, and the population spatial modeling of land use/cover data was carried out, which has higher simulation accuracy. (3) Among all kinds of topographic factors, the RDLS has a greater impact on the distribution pattern of population and economy, showing a significant negative correlation, and the impact of topographic relief on economic density is stronger than that of population density. (4) The agglomeration phenomenon of the population and economy tends to the lower RDLS area, moreover, the spatial agglomeration effect of economic development is stronger.