Meso-Cenozoic intracontinental orogenic processes in the Tian Shan orogenic belt have significant effect on the sandstone-hosted uranium deposits in the intramontane basins and those adjacent to the orogen. The Sawafuqi uranium deposit, which is located in the South Tian Shan orogenic belt, is investigated to reveal the relationships between uranium mineralization and orogenies. Recent exploration results show that the Sawafuqi uranium deposit has tabular, stratiform, quasi-stratiform, and lens-like orebodies and various geological characteristics different from typical interlayer oxidation zone sandstone-hosted uranium deposits. Systematic studies of ore samples from the Sawafuqi uranium deposit using a variety of techniques, including thin section observation, α-track radiograph, electron microprobe and scanning electron microscope, suggest that uranium mineralization is closely related to pyrite and organic matter. Mineralization-related alterations in the host rocks are mainly silicification and argillation including kaolinite, illite (and illite-smectite mixed layer) and chlorite. Tree stages of mineralization were identified in the Sawafuqi uranium deposit: (i) uranium-bearing detritus and synsedimentary initial pre-enrichment; (ii) interlayer oxidization zone uranium mineralization; and (iii) vein-type uranium mineralization. The synsedimentary uranium pre-enrichment represents an early uranium enrichment in the Sawafuqi uranium deposit, and interlayer oxidation zone uranium mineralization formed the main orebodies, which are superimposed by the vein-type uranium mineralization. Combining the results of this study with previous studies on the Meso-Cenozoic orogenies of South Tian Shan, it is proposed that the synsedimentary uranium pre-enrichment of the Sawafuqi uranium deposit was caused by Triassic Tian Shan uplift, and the interlayer oxidation zone uranium mineralization occurred during the Eocence-Oligocene period, when tectonism was relatively quiet, whereas the vein-type uranium mineralization took place in relation to the strong orogeny of South Tian Shan since Miocene.