The paper is devoted to the mineralogical and geochemical peculiarities and ore-forming conditions of the formation of the Kyzyl-Tashtyg pyrite-polymetallic deposit in Eastern Tuva. The ore mineral assemblages of the deposit were formed due to aqueous fluids containing Na, Mg, and K chlorides at the pressure of 900 bar and the variations of fO2, fS2, fSe2, and fTe2. The earliest pyrite ores in the central parts of the ore bodies were formed at relatively high temperatures of 400–260 °C due to a fluid of the composition NaCl-H2O and MgCl2-NaCl-H2O with the salinity of 4–11.3 wt% NaCl eq. The copper-zinc ores were deposited at 377–145 °C from the NaCl-H2O fluid with the salinity of 2.6–10 NaCl eq. and the copper ores – at 200–165 °C from the NaCl-KCl-H2O fluid with the salinity of 3.5–6.5 NaCl eq. The latest polymetallic and barite-polymetallic ores were formed at 330–130 and 270–140 °C, from the NaCl-KCl-H2O ± MgCl2-H2O fluid with the salinity of 3.5–8.8 and 2–8.5 wt% NaCl eq., respectively. The calculated δ34SH2S values of the fluid range from + 0.2 to + 6.6 ‰, which indicates the participation of sulfur of magmatic origin and borrowed from the host rocks. The δ34O isotopic composition of the fluid suggests that the fluid of magmatic genesis (+8.7… + 7.1 ‰) participated in the early stages of ore mineralization, and at the final stages, it was mixed with meteoric waters (-4.0…-0.7 ‰). The temperature decrease of mineral formation and fluid salinity from early to latest stages confirms the participation of heated meteoric waters. The results of the study of the geological structure, mineral assemblages, fluid inclusions, and stable isotope ratios provided to conclude that the formation of the Kyzyl-Tashtyg deposit was initiated by hydrothermal-magmatic activity, associated with the introduction of subvolcanic bodies of rhyolite and rhyolite-dacite and involvement of fluids separated during crystallization of felsic magma, as well as heated meteoric waters enriched with oxygen, which contributed to the growth of fO2 and variations fS2, fSe2, fTe2 and determined the diversity of mineral types of ores.