The Sichuan-Yunnan-Guizhou (SYG) metallogenic province, southwestern Yangtze Block, is one of the most important Zn-Pb repositories in China, with more than 200 million tons (Mt) of Zn-Pb ores. The source regions for the regional Zn-Pb mineralization in the SYG are still controversial, mostly in regard to the Emeishan flood basalts, basement rocks and host rocks. The Maozu Zn-Pb deposit is geographically close to the SYG center, which could also indicate that it is closer to the regional Zn-bearing fluid center than those deposits along the SYG margin. However, the origin of the ore-forming Zn in the Maozu deposit has not been constrained until now. In this study, the Zn and S isotopic compositions and Fe and Cd concentrations of the sphalerite from the Maozu deposit are investigated to evaluate the Zn isotopic fractionation during sphalerite precipitation, the source regions of the ore-forming zinc and sulfur, and the center of the regional Zn-bearing fluid system. It is suggested that the Zn isotopic fractionation between the sphalerite and original fluid during sphalerite precipitation could be limited due to the striking decrease in the temperature of the incoming fluid. The Zn isotopic variation of the sphalerite from four mining levels in the Maozu deposit is really small (-0.06 to +0.23 parts per thousand), which could be attributed to heterogeneous Zn isotopic compositions in original incoming fluid rather than Zn isotopic fractionation during sphalerite deposition. As such, in the Maozu deposit, the Zn isotopic compositions of original hydrothermal fluid could approximately be represented by the Zn isotopic signals documented in sphalerite (-0.06 to +0.23 parts per thousand). We found that the Zn isotopic signatures of incoming fluid are largely overlapped with those of the basement rocks (+0.10 to +0.34 parts per thousand), signifying that the ore-forming Zn could be predominantly sourced from the basement rocks. However, in the Maozu deposit, the ore-forming sulfur is most likely derived from the sulfur-bearing evaporates hosted in the country rocks via thermochemical sulfate reduction (TSR). The contrasting sources of ore-forming zinc and sulfur suggest the mixing of Zn-bearing fluid from the basement rocks and sulfur-bearing fluid from the host rocks, which could be responsible for the sharp decrease in the temperature of the incoming fluid in the Maozu deposit. Combined with the results of previous studies, the integrally lower Zn isotopic compositions of sphalerite in the Maozu deposit compared to those deposits along the SYG margin may demonstrate that the Maozu deposit is closer to the regional Zn-bearing fluid center. If this is the case, Zn isotopes could be an effective proxy to trace the Zn source of Zn-enriched ore deposits and to identify the regional Zn-bearing fluid center of Zn-enriched metallogenic provinces.