The Shitoukengde Ni-Cu deposit, located in the Eastern Kunlun Orogen, comprises three mafic–ultramafic complexes, with the No. I complex hosting six Ni-Cu orebodies found recently. The deposit is hosted in the small ultramafic bodies intruding Proterozoic metamorphic rocks. Complexes at Shitoukengde contain all kinds of mafic-ultramafic rocks, and olivine websterite and pyroxene peridotite are the most important Ni-Cu-hosted rocks. Zircon U-Pb dating suggests that the Shitoukengde Ni-Cu deposit formed in late Silurian (426–422 Ma), and their zircons have εHf(t) values of ?9.4 to 5.9 with the older TDM1 ages (0.80–1.42 Ga). Mafic-ultramafic rocks from the No. I complex show the similar rare earth and trace element patterns, which are enriched in light rare earth elements and large ion lithophile elements (e.g., K, Rb, Th) and depleted in heavy rare earth elements and high field strength elements (e.g., Ta, Nb, Zr, Ti). Sulfides from the deposit have the slightly higher δ34S values of 1.9–4.3‰ than the mantle (0 ± 2‰). The major and trace element characteristics, and Sr-Nd-Pb and Hf, S isotopes indicate that their parental magmas originated from a metasomatised, asthenospheric mantle source which had previously been modified by subduction-related fluids, and experienced significant crustal contamination both in the magma chamber and during ascent triggering S oversaturation by addition of S and Si, that resulted in the deposition and enrichment of sulfides. Combined with the tectonic evolution, we suggest that the Shitoukengde Ni-Cu deposit formed in the post-collisional, extensional regime related to the subducted oceanic slab break-off after the Wanbaogou oceanic basalt plateau collaged northward to the Qaidam Block in late Silurian.