The Yinjiagou pyrite-polymetallic deposit of Henan Province, located in the Huaxiong block of the southern margin of the North China craton, is the largest pyrite-polymetallic deposit in the East Qinling orogenic belt. The deposit is characterized by abundant pyrite resources and complicated paragenetic and associated elements, which is different from most molybdenum deposits characterized by Mo and W in the East Qinling area. From early to late, the ore-forming process can be divided into three periods of skarn, sulfide and epigenetic epochs, including seven ore-forming stages, representing as magnetite, vein quartz-molybdenite, quartz-pyrite-chalcopyrite-bornite-sphalerite, stockwork quartz-molybdenite, quartz-sericite-pyrite, calcite-galena-sphalerite and chalcedony-limonite stages, respectively. Three types of fluid inclusions are distinguished in quartz phenocryst, various quartz veins and calcite vein based on petrographic and microthemometric criteria, namely aqueous two-phase, CO2-bearing three-phase and daughter mineral-bearing multiphase inclusions. Fluid inclusions in quartz phenocryst of K-feldspar granite porphyry are mainly aqueous two-phase and daughter mineral-bearing multiphase inclusions with minor CO2-bearing three-phase inclusion, their homogenization temperatures and salinities vary from 341℃ to >550℃ and from 0.4% to 44.0% NaCl equivalent, respectively. Fluid inclusions in quartz of vein quartz-molybdenite stage are composed of aqueous two-phase and daughter mineral-bearing multiphase inclusions with homogenization temperatures and salinities vary from 382℃ to 416℃ and from 3.6% to 40.8% NaCl equivalent, respectively. Fluid inclusions in quartz and calcite of quartz-calcite pyrite-chalcopyrite-bornite-sphalerite stage consist of aqueous two-phase and daughter mineral-bearing multiphase inclusions, their homogenization temperatures and salinities vary from 318℃ to 436℃ and from 5.6% to 42.4% NaCl equivalent, respectively. Fluid inclusions in quartz of stockwork quartz-molybdenite stage are mainly composed of aqueous two-phase inclusion with minor daughter mineral-bearing multiphase inclusion, their homogenization temperatures and salinities vary from 321℃ to 411℃ and from 6.3% to 16.4% NaCl equivalent, respectively. Fluid inclusions in quartz of quartz-sericite-pyrite stage are aqueous two-phase and daughter mineral-bearing multiphase inclusions, with homogenization temperatures and salinities varying from 326℃ to 419℃ and from 4.7% to 49.4% NaCl equivalent, respectively. From skarn orebody to porphyry orebody, ore-forming temperature gradually reduces without evident salinity changes. The ore-forming fluid of the Yinjiagou deposit is characterized by high temperature and high salinity, roughly belonging to H2O-NaCl±CO2 system. The δ18OH2O values of the ore-forming fluid vary from 4.0‰ to 8.6‰, and δ18DV-SMOW values vary from -64‰ to -52‰, indicating that the ore-forming fluid was mainly derived from magmatic fluid. The δ18SV-CDT values of sulfides range from -0.2‰ to 6.3‰, with an average of 1.6‰, suggesting that the ore-forming material mainly came from deep sources and most likely came from lower crustal composed of poorly differential igneous material, in addition, the dolomite of the Guandaokou Group also provided part of the heavy sulfur. The 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios of 35 sulfide samples vary from 17.331 to 18.043, 15.444 to 15.575 and 37.783 to 38.236, respectively. These lead isotopic data are roughly consistent with those of the Yinjiagou intrusion occurring in the Yinjiagou ore district, implying that the ore lead of the Yinjiagou deposit was mainly originated from the felsic-intermediate intrusive rocks, with a small amount of lead from strata. To the conclusion, the Yinjiagou deposit belongs to porphyry-skarn deposit, the boiling action of ore-forming fluid is the dominant factor for metallic sulfide deposition, probably occurred in a transitional tectonic setting from nearly EW-trending to nearly NNE-trending tectonic regimes during the Mesozoic era.