Although carbonate rocks are important for carbonate-hosted PbZn deposits, there is no effective constraint on the role of carbonate rocks during the PbZn mineralization process. This paper uses the giant Huize PbZn deposit (>7 Mt. metals @ 25–35 % Pb + Zn) as a case study and employs zinc isotopes to gain new insights into such issue. The Huize deposit, located in the Sichuan-Yunnan-Guizhou (SYG) PbZn metallogenic province, is the largest carbonate-hosted deposit in the western Yangtze Block, SW China. Zinc isotope compositions of sphalerite, altered carbonate rocks and fresh carbonate rocks from the Huize deposit are of +0.39 ‰ to +0.68 ‰ (mean + 0.52 ‰, n = 20), −0.25 ‰ to +0.34 ‰ (mean + 0.07 ‰, n = 11) and + 0.35 ‰ to +0.71 ‰ (mean + 0.51 ‰, n = 6), respectively. The initial δ66Zn value of hydrothermal fluids calculated by the Rayleigh fractionation simulation is +0.4 ‰. Such zinc isotope signatures are significantly different from those of potential source rocks, such as the basement Proterozoic metamorphic rocks (δ66Zn = +0.10 ‰ to +0.34 ‰, mean + 0.22 ‰), the host Upper Ediacaran to Middle Permian sedimentary rocks (δ66Zn = −0.24 ‰ to +0.35 ‰, mean + 0.1 ‰) and the cover Upper Permian Emeishan basalts (δ66Zn = +0.30 ‰ to +0.44 ‰, mean + 0.35 ‰). Hence, it is likely that the carbonate rocks acted zinc source and provided heavy zinc isotopes for the PbZn mineralization. The ore-forming fluids extracted the heavy zinc isotopes of the ore-hosting carbonate rocks, resulting in the zinc isotopes of the altered carbonate rocks being far lighter than those of the marine carbonate rocks (δ66Zn = +0.24 ‰ to +1.32 ‰). The sulfur isotope compositions (+12.9 ‰ to +15.6 ‰, mean + 14.3 ‰, n = 20) of sphalerite from the Huize deposit also suggested that the source of reduced sulfur is the marine sulfate minerals within the ore-hosting carbonate rocks. Therefore, carbonate rocks play key roles in the formation of carbonate-hosted PbZn deposits: 1) provide ore-forming elements and ore-hosting space through dissolution; 2) cause isotope variation (e.g., zinc isotopes) by isotope exchange; 3) act as a carbonate buffer to adjust physicochemical conditions (e.g., pH) via cyclical carbonate dissolution, CO2 degassing and recrystallization. On the other hand, the zinc isotope mapping shows that the western part of the SYG PbZn metallogenic province has lighter zinc isotopes than those of the eastern part. This suggests that the migration pathway of hydrothermal fluids is likely west to east, which provides a new clue for regional PbZn ore prospecting. The outcomes have important benefits for understanding the genesis of PbZn deposits, the role of carbonate rocks and the application of zinc isotopes.