Abstract: The Tangjiazhai Pb-Zn deposit is located in the middle of the Longshan-Luota mining field in western Hunan Province, China, and is an important lead and zinc reserve base for Hunan Province. Sr isotope compositions measured for sphalerite were agecorrected by 372 Ma. As a result, the (⁸⁷Sr/⁸⁶Sr)_i values range from 0.70904 to 0.71143 with an average value of 0.70998(n=10) which is higher than that of the seawaterin the mineralized age (372 Ma), and lower than that of Lower Cambrian Shipai Formation shale enriched in organic matter. Speculation can be made is that Sr in ore-forming fluids is sourced from seawater (372 Ma) with relatively lower Sr contaminated high Sr Lower Cambrian Shipai Formation shale. Sphalerite and galena are measured for sulfur isotope composition. The δ³⁴S_V-CDT values of them have a range from 14.78‰ to 7.21‰ with a mean of 15.84‰ (n=9) which is lower 13.66‰ than that of the Early Ordovician seawater sulfate. This variation conforms to sulfur isotope fractionation of 10‰-20‰ when the mineralized temperature is from 100℃ to 200℃.These evidences indicate that the reduced sulfur in the sulfides probably derive from the Thermochemical Sulfate Reduction (TSR) of seawater sulfate within the ore-bearing strata.