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Fresh samples of basalts were collected by dredging from the Nanyue intraplate seamount in the Southwest sub-basin of the South China Sea (SCS). These are alkali basalts displaying right-sloping, chondrite-normalized rare earth element (REE) profiles. The investigated basalts are characterized by low Os content (60.37–85.13 ppt) and radiogenic 187Os/188Os ratios (~0.19 to 0.21). Furthermore, 40Ar/39Ar dating of the Nanyue basalts showed they formed during the Tortonian (~8.3 Ma) and, thus, are products of (Late Cenozoic) post-spreading volcanism. The Sr–Nd–Pb–Hf isotopic compositions of the Nanyue basalts indicate that their parental melts were derived from an upper mantle reservoir possessing the so-called Dupal isotopic anomaly. Semiquantitative isotopic modeling demonstrates that the isotopic compositions of the Nanyue basalts can be reproduced by mixing three components: the average Pacific midocean ridge basalt (MORB), the lower continental crust (LCC), and the average Hainan ocean island basalt (OIB). Our preferred hypothesis for the genesis of the Nanyue basalts is that their parental magmas were produced from an originally depleted mantle (DM) source that was much affected by the activity of the Hainan plume. Initially, the Hainan diapir caused a thermal perturbation in the upper mantle under the present-day Southwest sub-basin of the SCS that led to erosion of the overlying LCC. Eventually, the resultant suboceanic lithospheric mantle (SOLM) interacted with OIB-type components derived from the nearby Hainan plume. Collectively, these processes contributed crustal- and plume-type components to the upper mantle underlying the Southwest sub-basin of the SCS. This implies that the Dupal isotopic signature in the upper mantle beneath the SCS was an artifact of in situ geological processes rather than a feature inherited from a Southern Hemispheric, upper mantle source.