Gaocheng large-scale Pb-Zn-Ag deposit occurs in biotite granite in the western of Guangdong Province. A geochemical and isotopic study was carried out on the granitic rock in order to clarify its petrogenesis and explore tectonic implication. Overall, the geological, geochemical, and isotopic evidence suggests that the granitic rocks may have derived from the partial melting of old Proterozoic crust materials composed of sandstones with few mudstones. Combing with regional geological data, the Gaocheng biotite granite was likely intruded during the Caledonian collision process between Yangtze and Cathaysian plates.