High-temperature magma generation process and granulite-facies metamorphism can provide important information about mantle-crustal interaction and tectonic evolution. The strongly peralu-minous monzonite pluton, the Jinshuikou cordierite granite on the southern margin of the Qaidam Block, can provide important information about the mantle-crustal interaction and constraints on tectonic transition from Proto-Tethys to Paleo-Tethys. This pluton develops enclaves of mafic granulite, amphibolite and quartzofeldspathic rocks, and is cut by massive monzonitic leuco-granite veins. Zircon and monazite U-Pb dating for the cordierite granite, the granulite enclaves and a massive monzonitic leuco-granite vein reveal that the cordierite granitic magma was generated from Mesoproterozoic continental crust with protolith derived from a provenance that was composed of >2.8 Ga old recycled crustal materials and recorded a ~1.7 Ga magmatic event. The continental crust underwent low-pressure granulite-facies metamorphism at ~380 Ma ago, whereas the cordierite granite magmas was generated and emplaced during 380 Ma, followed by intrusion of the massive monzonitic leuco-granite vein at circa 370–330 Ma. These data suggest that after the final closure of Proto-Tethys Ocean spreading along the southern Qaidam Block at ~420 Ma, break-off of the subducted slab or delamination of the lower crustal base and upwelling of the asthenospheric mantle beneath the southern Qaidam Block occurred before the Mid-Devonian, and that the initiation of the Paleo-Tethys tectonics might initiate near the end of Early-Carboniferous in the East Kunlun-Qaidam region, East Asia.