The Shuiyindong gold deposit is one of the most famous and largest Carlin-type gold deposits in China and is located in southwest Guizhou, in the eastern part of the Huijiabao anticline. The Shuiyindong’s gold mineralization occurred in bioclastic limestone of the Permian Longtan Formation. Sulfur, carbon, hydrogen, oxygen, and lead isotopic compositions are reported in this paper. The properties and sources of ore-forming fluid have been discussed and a metallogenic model for the Shuiyindong gold deposit has been proposed. The d34 S values of stibnite, realgar, orpiment, pyrite from orebodies, and pyrite from quartz veins are similar to or slightly higher than the d34 S values of mantle sulfur. It is suggested that the sulfur of hydrothermal sulfides was likely of magmatic origin with minor heavy sulfur contributed from the country rocks. The measured d D values and calculated d18OH2 O values of inclusion fluid in quartz plotted within or below a magmatic hydrothermal fluid field far from the meteoric water line. This indicates that the ore-forming fluid for the main-stage gold mineralization could have been derived mainly from a magmatic source and mixed with a small amount of meteoric water. The carbon and oxygen isotopic compositions of calcites in the d18 O vs. d13 C diagram suggest that the CO2 in ore-forming fluid was derived from dissolution of bioclastic limestone and oxidation of sedimentary organic carbon in limestone. However, the d13 C values of ore-related calcites, which contain intergrown realgar and/or orpiment, are similar to those of mantle carbon. Although no igneous intrusive rock has been observed in the vicinity of the gold deposits, the possibility of mantle fluid integrated into the ore-forming fluid cannot be eliminated based on the d13 C values of ore-related calcites. The lead isotopes of sulfides are distributed near the growth curves of upper crust and orogenic belt in the plumbotectonic diagram. Their calculated Dc and Db values plotted within the magmatism field of crust-mantle subduction zone in the Dc- Db diagram. This suggests that the lead of sulfides has an intimate connection with magmatism. Our S, H, O, C, and Pb isotopic studies for the Shuiyindong Carlin-type gold deposit in Guizhou manifest a concordant possibility that the ore-forming fluid was mainly derived from magmatic fluid with minor contribution from the surrounding strata. With the integration of comprehensive geology and isotopic geochemistry, we have proposed a magmatic hydrothermal model for the origin of the Shuiyindong gold deposit. The Shuiyindong gold deposit is one of the most famous and largest Carlin-type gold deposits in China and is located in southwest Guizhou, in the eastern part of the Huijiabao anticline. The Shuiyindong’s gold mineralization occurred in bioclastic limestone of the Permian Longtan Formation. , carbon, hydrogen, oxygen, and lead isotopic compositions are reported in this paper. The properties and sources of ore-forming fluid have been discussed and a metallogenic model for the Shuiyindong gold deposit has been proposed. The d34 S values ​​of stibnite, realgar , orpiment, pyrite from orebodies, and pyrite from quartz veins are similar to or slightly higher than the d34 S values ​​of mantle sulfur. It is suggested that the sulfur of hydrothermal sulfides was likely of magmatic origin with minor heavy sulfur contributed from the country rocks . The measured d D values ​​and calculated d18OH2 O values ​​of inclusion fluid in quartz plotted or below a magmatic hydrothermal fluid field far from the meteoric water line. This indicates that the ore-forming fluid for the main-stage gold mineralization could have been derived mainly from a magmatic source and mixed with a small amount of meteoric water. The carbon and oxygen isotopic compositions of calcites in the d18 O vs. d13 C diagram suggests that the CO2 in ore-forming fluid was derived from dissolution of bioclastic limestone and oxidation of sedimentary organic carbon in limestone. However, the d13 C values ​​of ore-related calcites, which contain intergrown realgar and / or no, no similar to those of mantle carbon. Although no igneous intrusive rock has been observed in the vicinity of the gold deposits, the possibility of mantle fluid integrated into the ore-forming fluid can not be eliminated based on the d13 C values ​​of ore -related calcites. The lead isotopes of sulfides are distributed near the growth curves of upper crust and orogenic belt in the plumbotectonic diagram. Their calculated Dc and Db values ​​plotted within the magmatism field of crust-mantle subduction zone in the Dc-Db diagram. This suggests that the lead of sulfides has an intimate connection with magmatism. Our S, H, O, C, and Pb isotopic studies for the Shuiyindong Carlin- type gold deposit in Guizhou manifest a concordant that that ore-forming fluid was mainly derived from magmatic fluid with minor contribution from the surrounding strata. With the integration of comprehensive geology and isotopic geochemistry, we have proposed a magmatic hydrothermal model for the origin of the Shuiyindong gold deposit.