The origin of the Eocene shoshonitic rocks within the upper part of the extensive Linzizong volcanic succession (i.e., the Pana Formation) in the Gangdese arc, southern Tibet remains unclear, inhibiting the detailed investigations on the crust-mantle interaction and mantle dynamics that operate the generation of the coeval magmatic flare-up in the arc. We report mineral composition, zircon U–Pb age and zircon Hf isotope, whole-rock element and Sr–Nd–Hf isotope data for the Pana Formation volcanic rocks from Pangduo, eastern Gangdese arc in southern Tibet. The Pana volcanic rocks from Pangduo include basalts, basaltic andesites, and dacites. SIMS and LA-ICPMS zircon U–Pb dating indicates that the Pangduo dacites were erupted at 50±1 Ma, representing the volcanic equivalent of the coeval Gangdese Batholith that define a magmatic flare-up at 51±1 Ma. The Pangduo volcanic rocks are exclusively shoshonitic, differing from typical subduction-related calc-alkaline volcanic rocks. The basalts have positive whole-rock εNd(t) (+1.7) and εHf(t) (+3.8) with high Zr abundances (121–169 ppm) and Zr/Y ratios (4.3–5.2), most likely derived from the partial melting of an enriched garnet-bearing lithospheric mantle that was metasomatized by subduction-related components with input from asthenosphere. Compared to the basalts, similar trace elemental patterns and decreased whole-rock εNd(t) (–3.5 to –3.3) and εHf(t) (–2.5 to –1.6) of the basaltic andesites can be attributed to the input of the ancient basement-derived material of the central Lhasa subterrane into the basaltic magmas. The coherent whole-rock Sr–Nd–Hf isotopic compositions ((87Sr/86Sr)i = 0.7064–0.7069, εNd(t) = –6.0 to –5.2, εHf(t) = –5.6 to –5.0) and varying zircon εHf(t) (–6.0 to +4.1) of the dacites can be interpreted by the partial melting of a hybrid lower crust source (juvenile and ancient lower crust) with incorporation of basement-derived components. Calculations of zircon-Ti temperature and whole-rock zircon saturation temperature of the dacites, and clinopyroxene crystallization temperature of the basalts suggest that the Pangduo volcanic rocks are most likely derived from the high-temperature melting of the lithosphere (including lithospheric mantle and overlying continental crust) as a result of the slab breakoff of the Neo-Tethyan oceanic lithosphere.