Based on field investigation, microscopic and scanning electron microscopic observation, X-ray diffraction, microprobe analysis, salinity and composition measurement of fluid inclusions and isotopic composition measurement of S, O and H, the authors studied some genetic mineralogical properties of sphalerite from the Fankou Pb-Zn ore district in Guangdong Province. The results suggest that there are three generations of sphalerite in this ore district formed respectively at three stages of the hydrothermal Pb-Zn sulfide ore-forming period. These three generations of sphalerite show remarkable differences in such aspects as mode of occurrence, paragenesis, apparent color, morphology, cleavage development, unit cell parameter, Fe content, composition and salinity, δ18O％ and δD％ of fluid inclusions, δ34S‰ and fractionation equilibrium temperature with galena. The evolutional properties of the ore-forming fluid from the first stage to the third stage are as follows: the temperature and salinity varied from low through high to low again; the compositions of the ore-forming fluid changed from Na+-Ca+-Cl- through K+-Ca+-Cl- to Na+-Ca+-Cl- again. The values of δ18O, δD and δ34S decreased , but the decreasing was much more drastic from the second to the third stage than from the first to the second stage, implying that a portion of newly-produced solution with much lower values of δ18O, δD and δ34S participated in the ore-forming fluid during the third stage. It is thus held that the ore_forming fluid should be a kind of mixed-source hot brine heated by Yanshanian regional magmatic event, with a portion of magmatic-hydrothermal solution participating in the formation of the hot brine at the intermediate-late ore-forming stage