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Voluminous Early Cretaceous volcanic rocks in the central Lhasa subterrane provide an ideal opportunity for understanding the mantle–crust interaction and tectonic‐magmatic evolution of the Lhasa Terrane. Here, we report zircon U–Pb ages, geochemical and Sr–Nd–Pb–Hf isotopic data for the Early Cretaceous volcanic rocks, including high‐silica rhyolites (117.2 ± 1.1 Ma) and contemporaneous andesites (114.1 ± 0.8 Ma) in the Sailipu area, central Lhasa subterrane. All these rocks show enriched light rare earth elements (LREE), and radioactive heat‐generating elements (e.g., Th, U, K, and Pb) but depleted high‐field‐strength elements (HFSEs, e.g., Nb, Ta, P, and Ti). The different bulk‐rock Sr–Nd–Pb and zircon Hf isotopic compositions of the rhyolites and andesites suggest that these rocks have distinct magma sources and petrogenetic history rather than an identical source involving assimilation‐fractional crystallization process. The Sailipu high‐silica rhyolites exhibit the characteristics of fractional crystallization and have varying zircon εHf(t) values (−12.2 to +5.2), negative εNd(t) values (−9.5 to −1.6), high and variable initial Sr isotopic compositions ([87Sr/86Sr]i = 0.7047–0.7116) and radiogenic Pb isotopic signatures (206Pb/204Pb = 18.784–18.802, 207Pb/204Pb = 15.722–15.737, and 208Pb/204Pb = 39.382–39.492). A combined process of magma mixing (involving crustal‐derived felsic melts and mantle‐derived mafic melts) and subsequent fractional crystallization were mainly responsible for the formation of these high‐silica rhyolites. The Sailipu andesites show more enriched Sr–Nd isotopic compositions [(87Sr/86Sr)i = 0.7088–0.7154, εNd(t) = −9.9 to −6.7] relative to rhyolites, and less radiogenic Pb isotopic compositions (206Pb/204Pb = 18.632–18.669, 207Pb/204Pb = 15.686–15.689, 208Pb/204Pb = 39.140–39.201). They were likely derived from partial melting of an enriched mantle wedge previously metasomatized by melts derived from subducted sediments. We interprete these Early Cretaceous volcanic rocks as the product of slab break‐off during the southward subduction of the Bangong‐Nujiang Tethyan oceanic seafloor. The dominantly positive εHf(t) and ancient TDMC ages (0.85–1.90 Ga) of Sailipu high‐silica rhyolites further imply that, under the stress relaxation regime, the mantle‐derived melts locally reworked the ancient basement of the central Lhasa subterrane. [ABSTRACT FROM AUTHOR]