The Yadu Pb?Zn deposit is hosted in Permian limestone in the Sichuan-Yunnan-Guizhou (SYG) Pb-Zn metallogenic province, Southwest China. The ore genesis was investigated in this study based on rare earth element (REE) geochemistry and C, O, S, Pb, and Zn isotopes. The REE contents imply that basement fluid may has been one source of hydrothermal fluids, and the mineralization environment changed from acidic and reducing to alkaline and oxidizing during the mineralization process. The C and O isotopes show that the carbon in mineralizing fluids mainly comes from marine carbonate, and that basin fluid was one of the metallogenic fluids. S isotopic compositions (834S = +7.91?13.02%o) of sulfides revealed that S2- originated from high-solubility sulfate within the ore-hosting strata through thermochemical reduction (TSR) processes. The Pb isotopic ratios of sulfides (206Pb/204Pb = +18.7396?18.7542, 207Pb/204Pb = +15.7588?15.7616, and 208Pb/204Pb = +39.3817?39.4080) are similar to those of Proterozoic basement rocks in the region, and the Zn isotope values of sphalerite are relatively narrow, ranging from +0.53 to +0.65%o, close to that of the basement rocks (866Zn: +0.62%o); imply that the basement may have been the key source of mineralizing metals. In addition, the Zn isotope values showed an obvious linear relationship with Pb isotopic ratios, rather than the S isotope values, which suggests that the mineralizing metals and sulfur may have come from different sources. Based on comprehensive analysis of the geology, mineralogy, REE contents, and C?O?S?Pb?Zn isotopes, this study proposes that the mineralization of the Yadu Pb?Zn deposit may have resulted from mixing between basement fluid and basin fluid. According to the proposed model, the metal-rich fluids of the basement were driven into specific structural units of the sedimentary rocks (for example, fault?fold tectonic systems) and mixed with sulfate-rich fluids at the mineralization sites. Through TSR processes, there was continuous and abundant precipitation of hydrothermal minerals, which formed the high-grade Pb?Zn deposit. Overall, these geological and geochemical characteristics of the Yadu Pb?Zn deposit are consistent with those of the MVT deposits; thus we propose that the Yadu Pb?Zn deposit is MVT deposit, The determination of the genetic type of this deposit is conducive to the research and exploration of similar Pb?Zn deposits in SYG Pb?Zn metallogenic province.