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The widespread mid-Cretaceous igneous rocks in the northern margin of the Lhasa Block play an important role in understanding deep geologic processes, matter exchange at depth, and tectonic evolution of the Tibetan Plateau. In this paper, we report new zircon U-Pb ages, whole-rock major and trace element data, and Sr-Nd-Pb-Hf isotope data from the Talabuco andesites and basalts, which were dated at ~111 Ma. These rocks belong to the high-K calc-alkaline and shoshonite series, and show enrichment in terms of large-ion-lithophile elements (LILEs, e.g. Rb, U, and Th) and light rare earth elements (LREEs), but depletion of high-field-strength elements (HFSEs, e.g. Nb and Ti). The (87Sr/86Sr)iratios of the Talabuco andesites range from 0.7043 to 0.7048, and theεNd(t) contents range from 0.68 to 4.33. The ratios of206Pb/204Pb,207Pb/204Pb, and208Pb/204Pb are 18.6064–18.8993, 15.6233–15.6707, and 38.8634–39.1720, respectively. The176Lu/177Hf and176Hf/177Hf ratios of one sample range from 0.00081 to 0.00206 and 0.28280 to 0.28296, respectively. TheεHf(t) values for this sample range from 3.4 to 9.1, and the two-stage model Hf age (TDM2) is 0.59–0.95 Ga. Combined with previous studies, the geochemical and isotopic data reveal that the parental magma of the Talabuco andesites was probably derived by partial melting of EM II-type sub-continental lithospheric mantle (SCLM). The Talabuco andesites are most likely generated by fractionation of mafic magma contaminated by subducted oceanic sediment and represent product of arc magmatism due to northward subduction of the Yarlung Zangbo Neo-Tethyan slab or southward subduction of the Bangong Meso-Tethyan slab. [ABSTRACT FROM AUTHOR]