Granitoids at convergent plate boundaries can be produced either by partial melting of crustal rocks (either continental or oceanic) or by fractional crystallization of mantle-derived mafic magmas. Whereas granitoid formation through partial melting of the continental crust results in reworking of the pre-existing continental crust, granitoid formation through either partial melting of the oceanic crust or fractional crystallization of the mafic magmas leads to growth of the continental crust. This category is primarily based on the radiogenic Nd isotope compositions of crustal rocks; positive εNd(t) values indicate juvenile crust whereas negative εNd(t) values indicate ancient crust. Positive εNd(t) values are common for syn-collisional granitoids in southern Tibet, which leads to the hypothesis that continental collision zones are important sites for the net growth of continental crust. This hypothesis is examined through an integrated study of in situ zircon U-Pb ages and Hf isotopes, whole-rock major trace elements, and Sr-Nd-Hf isotopes as well as mineral O isotopes for felsic igneous rocks of Eocene ages from the Gangdese orogen in southern Tibet. The results show that these rocks can be divided into two groups according to their emplacement ages and geochemical features. The first group is less granitic with lower SiO2 contents of 59.82–64.41 wt%, and it was emplaced at 50–48 Ma in the early Eocene. The second group is more granitic with higher SiO2 contents of 63.93–68.81 wt%, and it was emplaced at 42 Ma in the late Eocene. The early Eocene granitoids exhibit relatively depleted whole-rock Sr-Nd-Hf isotope compositions with low (87Sr/86Sr)i ratios of 0.7044−0.7048, positive εNd(t) values of 0.6−3.9, εHf(t) values of 6.5−10.5, zircon εHf(t) values of 1.6−12.1, and zircon δ18O values of 5.28–6.26‰. These isotopic characteristics are quite similar to those of Late Cretaceous mafic arc igneous rocks in the Gangdese orogen, which indicates their derivation from partial melting of the juvenile mafic arc crust. In comparison, the late Eocene granitoids have relatively lower MgO, Fe2O3, Al2O3, and heavy rare earth element (HREE) contents but higher K2O, Rb, Sr, Th, U, Pb contents, Sr/Y, and (La/Yb)N ratios. They also exhibit more enriched whole-rock Sr-Nd-Hf isotope compositions with high (87Sr/86Sr)i ratios of 0.7070−0.7085, negative εNd(t) values of −5.2 to −3.9 and neutral εHf(t) values of 0.9−2.3, and relatively lower zircon εHf(t) values of −2.8–8.0 and slightly higher zircon δ18O values of 6.25–6.68‰. An integrated interpretation of these geochemical features is that both the juvenile arc crust and the ancient continental crust partially melted to produce the late Eocene granitoids. In this regard, the compositional evolution of syn-collisional granitoids from the early to late Eocene indicates a temporal change of their magma sources from the complete juvenile arc crust to a mixture of the juvenile and ancient crust. In either case, the syn-collisional granitoids in the Gangdese orogen are the reworking products of the pre-existing continental crust. Therefore, they do not contribute to crustal growth in the continental collision zone.