When it comes to Pb-Zn ores with high amounts of pyrite, the major problem encountered is the low separation efficiency between galena and pyrite. By virtue of high dosage of lime and collector sodium diethyl dithiocarbamate (DDTC), pyrite and zinc minerals are depressed, allowing the galena to be floated. However, there have been significant conflicting reports on the flotation behavior of galena at high pH. In this context, correlation of the surface adsorption and oxidation with the floatability difference of galena and pyrite in high-alkaline lime systems would be a key issue for process optimization. Captive bubble contact angle measurements were performed on freshly polished mineral surfaces in situ exposed to lime solutions of varying pH as a function of immersion time. Furthermore, single mineral microflotation tests were conducted. Both tests indicated that the degree of hydrophobicity on the surfaces of galena and pyrite increased in the presence of DDTC at natural or mild pulp pH. While in a saturated lime solution, at pH 12.5, DDTC only worked for galena, but not for pyrite. Surface chemistry analysis by time-of flight secondary ion mass spectrometry (Tof-SIMS) confirmed the preference of DDTC on the galena surface at pH 12.5, which contributed to a merit recovery. Further important evidence through measurements of Tof-SIMS, ion chromatography, and highperformance liquid chromatography indicated that in high-alkaline lime systems, the merit floatability of galena could exclude the insignificant contribution of elemental sulfur (S-8) and was dominantly attributed by the strong adsorption of DDTC. In contrast, the poor flotation response of pyrite at high pH was due to the prevailing adsorption of CaOH+ species. This study provides an important surface chemistry evidence for a better understanding of the mechanism on the better selectivity in the galena-pyrite separation adopting high-alkaline lime systems.