The Bafangshan-Erlihe large Zn-Pb-Cu deposit is located in the northern part of the Fengxian-Taibai (abbr. Fengtai) ore cluster, west Qinling orogen, whose genesis remains controversial, and the viewpoints can be summarized in two leading models: a SEDEX or sedimentary-reformed deposit model, and an epigenetic hydrothermal deposit model. In this work, detailed observations of deposit geology and systematic study of ore-forming fluids have been carried out to provide a further understanding of the ore genesis.The major orebody forms in saddle shape within the NWW-trending Bafangshan-Erlihe anticline core, in the contact zone between Middle Devonian limestone and Upper Devonian phyllite. The deposit contains well-developed multi-stage quartz-sulfide veins, with intense hydrothermal alterations within both the roof and the floor rocks. Three stages of mineralization have been recognized: stage I, a sphalerite-rich massive sulfide stage; stage II, a polymetallic sulfide quartz vein stage; and stage III, a carbonate-sulfide quartz vein stage. Ore minerals, including sphalerite, galena, pyrite and chalcopyrite, commonly occur as medium to coarse grains rather than cryptocrystalline aggregates. All of the above characteristics indicate an epigenetic origin of the Zn-Pb-Cu mineralization.Fluid inclusion microthermometric and laser Raman spectroscopic analyses presented in this study show that the ore fluids have low to moderate salinities (0.6–18.5 wt% NaCl), and contain a significant amount of CO2 and hydrocarbons (e.g., methane). Fluid inclusion total homogenization temperatures range from 98 to 451 °C. Analyses of hydrogen and oxygen isotopes in quartz from the three mineralization stages indicate that the mixture of organic, magmatic and/or metamorphic waters has contributed to the formation of stage I mineralization, while magmatic water dominates during stage II mineralization, and meteoric water is involved during stage III mineralization. Mixing of organic-rich metamorphic fluid (or basinal brines) with low to moderate temperature and high temperature magmatic fluid occurred throughout the mineralization processes. Fluid immiscibility probably caused the release of a large amount of CO2 and/or hydrocarbons during mineralization stages I and II, and subsequently resulted in the precipitation of sulfides.By combining evidence from our new analytical results and those of previous studies in the context of the regional geology, we propose an epigenetic hydrothermal origin of the Bafangshan-Erlihe Zn-Pb-Cu deposit, and suggest that the mineralization is the result of vein-filling and hydrothermal alteration of low-moderate temperature fluids derived from multiple sources. The hydrothermal ore-forming system was probably driven by Late Triassic regional tectono-magmatic activity associated with the South Qinling collisional orogeny.