The Shuikoushan ore district, located in southern Hunan Province, South China, contains Pb–Zn–Au mineralization hosted in the Devonian to Triassic strata and Mesozoic granodiorite intrusions. Ore minerals are mainly pyrite, sphalerite, galena and minor molybdenite. Molybdenite, usually intergrown with pyrite, formed during Pb–Zn hydrothermal mineralization. In order to determine the precise age of Pb–Zn mineralization and further understand the relationship between magma emplacement and hydrothermal mineralization in the ore district, molybdenite Re–Os dating and zircon SIMS U–Pb dating were undertaken. The zircon U–Pb dating reveals that the granodiorite intrusion was emplaced at 158.8 ± 1.8 Ma (MSWD = 0.40). Re–Os isotopic age of seven molybdenite samples yields model ages ranging from 157.5 ± 2.5 Ma to 161.0 ± 2.4 Ma, and gives a well-defined 187Re–187Os isochron age of 157.8 ± 1.4 Ma (2σ, MSWD = 1.3), indicating the timing of Pb–Zn mineralization in the Shuikoushan ore district at about 158 Ma. This date coincides well with the zircon SIMS U–Pb age of the granodiorite, revealing a genetic association between the Pb–Zn mineralization and the granitic magmatism. Combined with geochronological data published for other Pb–Zn–(Cu) deposits in southern Hunan, it can be concluded that the granodiorite-related Pb–Zn mineralization throughout southern Hunan mainly occurred at 160–156 Ma, rather than 180–170 Ma or 170–160 Ma as considered previously. The Pb–Zn mineralization and major W–Sn mineralization in southern Hunan are coeval and may be related to the same geological event.