The Hongtaiping Cu-Pb-Zn deposit is located in the central part of the Yanbian-Dongning region, NE China, which is the eastern segment of the Central Asian Orogenic Belt. The Cu-Pb-Zn mineralization occurs in the contact zone of the Lower Permian Miaoling and Kedao formations with tuff lavas, tuffs, and marlstones as the principal host rocks. The orebodies are distributed in stratiform, stratiform-like and lenticular morphologies, consistent with the host strata. Field investigations indicate three ore facies consisting of stringer-stockwork, massive, and laminated ores in the Hongtaiping deposit, which show apparent variation spatially from bottom to top of sulphide types. A lot of liquid-rich fluid inclusions were identified in mineral crystals from the three types of ore facies with complete homogenization temperatures varying from 162 to 249 degrees C and salinities in the range of 3.3 to 9.6 wt% NaCl equiv. The delta D and 18OH2O values of calcite samples from the stringer or stockwork ores range from -82.0 to -75.1 parts per thousand and 3.3 to 3.7 parts per thousand, respectively, lower than those (delta D values of -64.1 to -38.8 parts per thousand, 18OH2O values of -0.9 to 2.2 parts per thousand) of the massive and laminated ores. In addition, the calcite samples show restricted delta C-13 values from -6.8 to -4.0 parts per thousand. These fluid inclusions and H-O-C isotope geochemistry suggest that ore-forming fluids of the Hongtaiping deposit were mainly sourced from heated seawater or brine derived, with the carbon from marine carbonates by water-rock interaction. The delta S-34 values of sulphide separates from the stringer-stockwork, massive and laminated ores range from -15.2 to -9.2 parts per thousand with an average value of -12.3 parts per thousand. The sulphide minerals yield Pb-206/Pb-204 ratios from 18.025 to 19.758, Pb-207/Pb-204 ratios from 15.601 to 15.795, and Pb-208/Pb-204 ratios from 37.202 to 39.305. These S and Pb isotope compositions indicate that the sulphur had an origin in seawater sulphates from which sulphur was most possibly transformed into sulphide by thermochemical reduction, while the lead in ores originated mainly from the Miaoling Formation, with small amounts directly derived from the subvolcanic intrusion. Taken together, the Hongtaiping deposit can be classified as a volcanogenic massive sulphide (VMS) deposit, for which the possible mineralization process is interpreted in terms of a long-lived convective circulation of mobile heated seawater mixed with some magmatic fluids along submarine faults and fissures during the Early Permian. The metals were migrated and subsequently enriched in the hydrothermal circulation system by being leached from the underlying volcanic rocks, with the metal-rich ore-forming fluids combined with contributions of water-rock reaction, thermochemical sulphate reduction and temperature change leading to the precipitation of polymetallic sulphides.