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The tectonic inversion of the Songliao Basin during the Cenozoic may have played an important role in controlling the development of sandstone-type uranium deposits. The widely distributed mafic intrusions in the host sandstones of the Qianjiadian U ore deposits provided new insights to constrain the regional tectonic evolution and the genesis of the U mineralization. In this study, zircon U-Pb dating, whole-rock geochemistry, Sr-Nd-Pb isotope analysis, and mineral chemical compositions were presented for the mafic rocks from the Qianjiadian area. The mafic rocks display low SiO2 (44.91–52.05 wt.%), high TFe2O3 contents (9.97–16.46 wt.%), variable MgO (4.59–15.87 wt.%), and moderate K2O + Na2O (3.19–6.52 wt.%), and can be subdivided into AB group (including basanites and alkali olivine basaltic rocks) and TB group (mainly tholeiitic basaltic rocks). They are characterized by homogenous isotopic compositions (εNd (t) = 3.47–5.89 and 87Sr/86Sr = 0.7032–0.7042) and relatively high radiogenic 206Pb/204Pb (18.13–18.34) and Nb/U ratios (23.0–45.6), similar to the nearby Shuangliao basalts, suggesting a common asthenospheric origin enriched with slab-derived components prior to melting. Zircon U-Pb and previous Ar-Ar dating show that the AB group formed earlier (51–47 Ma) than the TB group (42–40 Ma). Compared to the TB group, the AB group has higher TiO2, Na2O, K2O, P2O5, Ce, and HREE contents and Ta/Yb and Sr/Yb ratios, which may have resulted from variable depth of partial melting in association with lithospheric thinning. Combined with previous research, the Songliao Basin experienced: (1) Eocene (~50–40 Ma) lithospheric thinning and crustal extension during which mafic rocks intruded into the host sandstones of the Qianjiadian deposit, (2) a tectonic inversion from extension to tectonic uplift attributed to the subduction of the Pacific Plate occurring at ~40 Ma, and (3) Oligo–Miocene (~40–10 Ma) tectonic uplift, which is temporally associated with U mineralization. Finally, the close spatial relation between mafic intrusions and the U mineralization, dike-related secondary reduction, and secondary oxidation of the mafic rocks in the Qianjiadian area suggest that Eocene mafic rocks and their alteration halo in the Songliao Basin may have played a role as a reducing barrier for the U mineralization. [ABSTRACT FROM AUTHOR]