Situated at the southwestern margin of Yangtze Landmass, the Nayongzhi Pb-Zn deposit is a large-sized ore deposit (>1.30Mt) recently found in the Wuzhishan anticline, and also is the largest within the Sichuan-Yunnan-Guizhou ore cluster area in Guizhou province now. Obviously controlled by the stratabound and structures, the ore bodies of this deposit occur as stratiform-like, vein-like and lentiform in bedding structural zones at the southeast flank of the Wuzhishan anticline. And the hosted rocks are dominated by dolostone of Lower Cambrian Qingxudong and Upper Sinian Dengying formations. Both gently-inclined stratoid and steeply-dipped veined orebodies are characterized by well-developed brecciated, veined, reticular-veined, and disseminated structures. The main metal mineral is sphalerite, with galena and pyrite as secondary ore minerals. Gangue minerals are dominated by dolomite and calcite, with minor amount of quartz and barite. The research result indicates that δ34SVCDT values of the sulfides range from +4.7‰ to +22.8‰ with an average of +16.68‰. Most of the samples have 34S values within +18‰~+22.5‰, significantly higher than δ34S value of the orehosting dolostone as +7.3‰. The overall trend of δ34S Sphalerite>δ34S Galena>δ34SPyrite shows a non-equilibrium fractionation of sulfur isotope, indicating that the total sulfur of the oreforming fluid, i.e. δ34S∑S, should be greater than the mean δ34S value of the sulfides as +16.68‰. Therefore, that the sulfur in the ore-forming fluid was dominantly sourced from the evaporation cream rock in the marine carbonatite and the product of Thermal-chemical Sulfate Reduction (TSR). The Pb isotope compositions of the sulfides shows the normal lead composition characteristics, ranging 17.8240~17.9701, 15.6364~15.7651 and 37.8956~38.3230 respectively for 206Pb/204Pb, 207Pb/204Pb and 208Pb/204 Pb, and this is a little different from that of the ore-hosting dolostone. However, distinct crust-derived nature suggests that the Pb metal was likely derived from regional basement rocks. In conclusion, the Nayongzhi PbZn deposit is controlled by strata and faults, with oreforming material from crustal source rocks. Sulfide precipitation was controlled by the mixing effect of the metal-rich fluid and rich reductive fluid, and was the product of the coupling of regional tectonics and largescale ore-forming fluids. Therefore, the Nayongzhi Pb-Zn deposit belongs to an MVT ore deposit.