The Fozichong ore district, located in the southern segment of the Qinghang metallogenic belt, is a large-sized Pb-Zn polymetallic deposit in South China. This study presents new data on fluid inclusions and H-O-S-Pb isotopic compositions from the ore bodies in the Guyi deposit of the Fozichong ore district. Analysis of the fluid inclusions reveal that the early sulfide-forming stage (Stage I) is characterized by various types of the fluid inclusions, including the daughter mineral containing type, the CO2-H2O type and the H2O type, but both the main sulfide-forming stage (Stage II) and the late sulfide-forming stage (Stage III) are dominated by the H2O type. From the early to the late stage, the ore-forming fluids were changed from high-moderate temperature and high salinity to moderate-low temperature and low salinity. Hydrogen isotopic compositions (delta D) from - 59 parts per thousand to - 41 parts per thousand), oxygen isotopic compositions (delta O-18(H2O) from -5. 47 parts per thousand to 4. 00 parts per thousand) and chemical components of the fluid inclusions indicate the initial ore-forming fluids were sourced from the magmatic fluid, and mixed with the meteoric water in later process. Sulfur isotopic compositions (delta S-34 from 2. 3 parts per thousand to 4. 3 parts per thousand) indicate that the sulfur was mainly derived from the felsic magmatic system. The Pb isotopic compositions (Pb-206/Pb-204 of 18. 592 similar to 18. 794, Pb-207/Pb-204 of 15. 648 similar to 15. 864, Pb-208/Pb-204 of 38. 909 similar to 39. 580) reveal that the ore-forming metals were sourced from both the felsic magmatic system and the country rock strata. The formation of the Fozichong Pb-Zn deposit has close association with the granite porphyry intruded in the Late Yanshanian Period (106Ma), and it can be classified as the magmatic-hydrothermal type Pb-Zn deposit. The Hesan and Guyi ore deposits in the Fozichong ore district represent products of the near-source high-moderate temperature magmatic hydrothermal mineralization and the far-source moderate-low temperature hydrothermal mineralization, respectively.