Metal stable isotopes (e.g., Zn, Cd, and Cu) have been used to track metal sources in differenttypes of hydrothermal systems. However, metal isotopic variations in sulphides could be triggered by variousfactors such as mineral precipitation and fluid mixing. Thus, tracking the metal sources of hydrothermalsystems is still a big challenge for metal isotopes. In this study, we investigated the Cd isotopic systematics ofsphalerite from the Nayongzhi Zn–Pb deposit, which is a Mississippi Valley‐type (MVT) deposit in theSichuan–Yunnan–Guizhou mineralization province (SYGMP). We reinterpreted the published S isotope datafor the SYGMP and found that the large S isotopic variations were controlled by Rayleigh fractionationbetween sulphide and reduced S. As such, a model that involves mixing of a metal‐rich fluid with a reduced Spool formed by thermochemical sulfate reduction (TSR) can explain the ore formation in the Nayongzhideposit. Based on this model, no Cd isotopic fractionation was observed due to its low solubility in fluidsduring mixing, and thus the Cd isotopic variations of sphalerite were inherited from the source rocks. Thelarge range of Zn/Cd ratios and uniform Cd isotopic compositions of the sulphides are similar to those ofigneous rocks but different from those of sedimentary rocks, indicating that Zn and Cd were derived mainlyfrom basement rocks (e.g., migmatite, gneiss, and granulite). Our results reaffirm that metal stable isotopes,particularly Cd isotope compositions of sphalerite, are powerful geochemical tracers for investigating theformation mechanisms of ore deposits。