Revealing hydrothermal evolution (from the early quartz-sulfide to the late fluorite-carbonate-sulfide stages) of skarn sulfide deposits is significant for understanding their ore formation processes, but the detailed studies are rare. In this study, we choose the Dongzhongla skarn Pb-Zn deposit (0.38 Mt Pb + Zn) located in central Lhasa, Tibet as a case study, and present detailed ore deposit geology and dataset of in situ chemical compositions of quartz, in situ Pb isotopic ratios of galena, sulfur isotopic compositions of sulfides and C-O isotopic compositions of hydrothermal calcite and wall rocks to address this issue. There are two types of hydrothermal quartz in the early stage: (1) the early phase euhedral quartz (Qz1) crosscut by quartz-sulfide veins, and (2) the late phase subhedral quartz (Qz2) coexisting with sulfides. TitaniQ thermometer of Qz1 and Qz2 limits the two phases with a temperature range of 336-427 degrees C (mean 373 degrees C) and 357-461 degrees C (mean 386 degrees C), respectively. The decreasing Al concentrations of Qz1 from core to rim suggest that magmatic fluids mixed with acidic meteoric water prevented the precipitation of sulfides during the early phase. The increasing Al and decreasing sulfur concentrations of Qz2 indicate that the increasing pH values of hydrothermal fluids made principal sulfides precipitate during the late phase. In addition, fluid inclusions and C-O isotopic studies reveal that the late stage minerals were deposited from low salinity (< 2 wt% NaCl equiv.) fluids at 250-300 degrees C. The rock/water (R/W) ratios for fluids were 0.2-1, whereas the water/rock (W/R) ratios for wall rocks were up to similar to 10. The delta S-34 values range from 2.13 to 3.99 parts per thousand, indicating a magmatic origin of sulfur. The Pb isotopic ratios are consistent with those of the early Cretaceous felsic intrusions and those of the Lhasa basement, suggesting that the source of Pb is associated with the early Cretaceous magmatism, which was generated by partial melting of the Lhasa basement. The in situ Pb isotopes also reveal that Pb derived from wall rocks can be negligible, although the W/R interaction accounts for the precipitation of sulfides. Hence, the hydrothermal evolution of the Dongzhongla skarn Pb-Zn deposit went through: (1) acidification process, i.e. magmatic fluids mixed with acidic meteoric water, which may restrain the precipitation of sulfides in the early phase, and (2) neutralization process, i.e. oreforming fluids occurred at different degrees of W/R interaction during late phase, which is in favor of Pb-Zn mineralization.