Early to mid-Paleozoic tectonothermal events in the Qilian Orogen developed during the closure of the Proto-Tethys Ocean and the convergence of microcontinents in the periphery of East Gondwana. In this paper, we present geochronological, geochemical and Sr–Nd-Hf isotopic data for the granitoid rocks and mafic dykes in southeastern Qilian Orogen. The Liwan (440 Ma), Shixia (434 Ma) and Huchuan (429 Ma) granitoid rocks have metaluminous to weakly peraluminous features, with whole-rock ε Nd ( t ) values of 1.1 to 1.6, −4.2 to −4.4 and −2.6 to 1.1, and zircon ε Hf ( t ) values of 0 to 8.9, −6.6 to 1.6 and −4.6 to 2.2, respectively. Geochemical data suggest that the Liwan, Shixia and Huchuan granitoids are derived from partial melting of the Proterozoic basement with addition of juvenile material, felsic crustal basement and mafic crustal material, respectively. The Zhangjiayuan mafic dykes (403 Ma) are high-K to shoshonitic with whole-rock ε Nd ( t ) (−1.1 to −0.9) and zircon ε Hf ( t ) values (−0.9 to 13.3), derived from an enriched lithospheric mantle. We suggest that these Silurian–Early Devonian intrusive rocks were formed via complex events involving arc-related subduction followed by slab-tearing to post-collisional processes during the Silurian and subsequent lithospheric extension in the Early Devonian. Supplementary material: Tables giving zircon U–Pb isotopic data, whole-rock major and trace element results, whole-rock Sr–Nd isotopic data and zircon in situ Lu–Hf isotopic data are available at https://doi.org/10.6084/m9.figshare.c.6693575