Mineral resources in South China are abundant with the distribution of multiple polymetallic metallogenic belts. The formation of polymetallic metallogenic belts was often accompanied by a special deep background and the underground process. Studying the crust-mantle coupling relationship reflected by the crustal thickness based on the Moho depth calculation can provide a reference for exploring the formation and evolution of underground massive metal resources in South China. In this paper, the data of high-order satellite gravity field model EIGEN-6C4 was corrected based on the gravity calculation method of spherical coordinates, and the satellite Bouguer gravity anomaly was obtained in South China. Then the modified Parker-Oldenburg method was used to perform the variable density interface inversion, and the characteristics of the Moho surface in South China were revealed. Finally, based on the ranges of different metallogenic belts in the area and the geological and geochemical data available, the authors investigated the relationship between the source of ore-forming materials and the formation mechanism of Moho surface undulations in different metallogenic belts in the study area. It is estimated that the middle and lower reaches of the Yangtze River and the eastern part of the Qinhang area are located in the metallogenic belt of the Moho surface uplift area. In addition, mantle source materials played a dominant role in its metallogenesis, forming a polymetallic deposit mainly composed of copper and iron. The Nanling, Wuyi, western section of Qinhang and western Hubei-Xiangxi are located in the metallogenic belt of the Moho facetocclusion zone. The ore-forming process was closely linked to the interaction of the shell and mantle source, forming tungsten, tin, gold and silver, lead and zinc and other polymetallic deposits.