The East Qinling region in central China, hosting several tens of Mesozoic magmatic-hydrothermal Mo deposits, is one of the largest molybdenum belts in the world. The Zhifang Mo deposit is hosted in volcanic rocks of the Xiong'er Group in the Waifangshan area, Qinling Orogen. Previous studies variously correlated the mineralization in this deposit with Yanshanian magmatism or Palaeo-Mesoproterozoic volcanic-hydrothermal events. The orebodies are associated with quartz veins and controlled by subsidiary faults of the Machaoying Fault. The ore-forming process can be divided into the early, middle and late stages and is characterized by quartz-pyrite, quartz-polymetallic sulphide and quartz-carbonate veins, respectively. The early-stage quartz is structurally deformed, suggesting a compressional tectonic regime; the middle-stage sulphides fill the fractures of the early-stage assemblages and show no deformation, suggesting a tensional setting; the late-stage veins mostly infill the open-space fissures. Three types of fluid inclusions (FIs) are identified at the Zhifang deposit: H2O-NaCl (W-type), CO2-rich (C-type) and daughter mineral-bearing inclusions (S-type). Fluid inclusions of early-stage quartz homogenize between 380 and 470 °C, with salinities ranging from 0.4 to 9.6 wt.% NaCl equiv., whereas the late-stage calcite contains only the W-type FIs with homogenization temperatures of lower than 240 °C, and salinities of 0.4–8.7 wt.% NaCl equiv. This indicates that the ore fluid system evolved from CO2-rich, probably metamorphic hydrothermal to CO2-poor, meteoric fluid. All three types of FIs can be observed in the middle-stage quartz, and even in the microscopic domain of a crystal, suggesting that this heterogeneous association was trapped from a boiling fluid system. These FIs homogenized at temperatures ranging from 250 to 360 °C and display two salinity clusters of <18.5 and 29.1–29.9 wt.% NaCl equiv. These results suggest that metal precipitation resulted from fluid boiling. The estimated trapping pressures of FIs range from 101 to 285 MPa, suggesting an alternating lithostatic–hydrostatic fluid system, which was controlled by a fault-valve at the depth of 10 km. The δ34S values of ore minerals from the Zhifang Mo deposit show a range between −11.8‰ and 6.0‰, with a bimodal distribution. The early-stage pyrite has a positive δ34S value of 6.0‰ that is similar to the host rocks of the Xiong'er Group and the Taihua Supergroup, suggesting that the wall rocks contributed much of the sulphur to the early-stage pyrite during fluid–rock interaction. However, the δ34S values of the middle-stage sulphides have negative mean and restricted range from −11.8‰ to −4.5‰. The widespread rutile grains coexisting with molybdenite in the middle-stage correlate the negative δ34S values with relatively oxidized fluids. We consider phase separation as an efficient mechanism for ore-fluid oxidation and molybdenum deposition based on fluid inclusions and sulphur isotope data. Geological, fluid inclusion and sulphur isotope data of the Zhifang Mo deposit suggest that the Mo mineralization is unrelated to the Yanshanian magmatism or the Palaeo-Mesoproterozoic volcanic-hydrothermal event. Here we propose that the Zhifang Mo deposit may be considered as an orogenic mineral system, with its formation in an active continental margin related to the northward subduction of the Mian-Lue oceanic plate during the Triassic. Copyright © 2014 John Wiley & Sons, Ltd.