In this paper, we conducted systematically zircon LA-ICP-MS UP-b dating, Lu-Hf isotopic analyses and wholerock geochemical analyses for two granitic plutons (Dongga granitic pluton and Numa granitic pluton), and elucidated their petrogenesis and tectonic setting in the middle Gangdese batholith, southern Tibet. The Dongga granitic pluton is mainly composed of quartz and feldspar, with minor amount of biotite and hornblende. The Numa granitic pluton consists of quartz and feldspar dominantly as well as minor amount of biotite. The zircon UP-b dating yielded a mean age of 185.8±2.3 Ma for the Dongga pluton and two mean ages of 185.9±2.2 Ma and 185.1±1.7 Ma for the Numa pluton. The results show the similar diagenesis ages, indicating they were the products of the simultaneous magmatic event in the Gangdese batholith, southern Tibet. Geochemically, two granitic plutons show enrichment of LREE and LILE as well as depletions of HFSE (Nb, Ta and Ti), suggesting a subductionrelated tectonic setting. Rittmann and Aluminium saturation signatures suggest that those two granitic plutons belong to typical calcalkaline and weak peraluminous (A/CNK) Itype granite. Zircon Hf isotopic components demonstrate that the Dognga and Numa plutons are characterized by highly depleted Hf isotopic compositions and young second model ages (tDM2), with the εHf(t) values of +11.14~+15.55 (mean value +13.76) and +9.49~+15.52 (mean value +1356), respectively, indicating that the granitic plutons originated from partial melting of juvenile crustal materials. During the partial melting, underplating mantle magma played a key role in causing the partial melting of the lower crustal juvenile materials in the Gangdese belt. Integrated study, along with previous studied results, indicates that the granitic plutons were generated in an active continental margin arc setting related to the northward subduction of the NeoTethys oceanic crust beneath the Lhasa terrane during the Early Jurassic (Pliensbachian stage) in the Gangdese belt, southern Tibet.