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The northward subduction of the Neo-Tethys oceanic lithosphere and subsequent collision between India and Asia continents gave rise to the Tibetan Plateau. However, how and when oceanic subduction started to transform to an intraplate environment are still open questions. The granitoids distributed in Lhasa Terrane of south Tibet offer a unique chance for us to investigate the deep geodynamic processes. Here, we present zircon U–Pb–Hf isotope, whole-rock major and trace element and Sr–Nd isotope data of granitoid intrusions in the Sangsang area of the southern Lhasa Terrane. The Sangsang granodiorites and granites were crystallized at ca. 54 Ma, while the emplacement age of the quartz monzonites is ca. 47 Ma. The granodiorites are characterized by relatively high Mg# values (35.3–41.1) and Fe2O3t (5.16–6.26 wt%) contents, and low Na2O + K2O contents (6.4–6.9 wt%) and A/CNK values (0.91–0.99), which are similar to the geochemical characteristics of I-type, high-K calc-alkaline rocks. They have high 87Sr/86Sri ratios (0.706455–0.706490), and low εNd(t) (− 3.58 to − 2.96) and zircon εHf(t) (− 3.4 to 0.3) values, indicating they were derived from a hybrid source of ancient mafic crust and juvenile lower crust. The coeval granites have lower Mg# values (22.5–27.25) and similar zircon εHf(t) values (− 2.6 to 1.1), suggesting they were probably differentiation productions of the granodiorites. The quartz monzonites have higher Na2O + K2O contents (9.18–9.59 wt%) and A/CNK values (0.98–1.03), higher zircon εHf(t) values (− 2.2 to 2.6) and more depleted Sr and Nd isotopes than the granodiorites and granites. The quartz monzonites were probably produced by melting of mixed juvenile crustal materials and metagreywacke. The new geochronological and geochemical data help constrain the geodynamic processes in the Lhasa Terrane during the Early Cenozoic, as the Sangsang granitoids represent the change from subduction termination to intraplate extension at the southern margin of the Lhasa Terrane. [ABSTRACT FROM AUTHOR]