Hydrothermal alteration records fluid–rock interactions and can therefore be used to constrain element migrations during mineralization. Although hydrothermal alteration is widely developed in hydrothermal vein-type uranium deposits in South China, consideration of elemental mass changes during alteration has not been examined. The Egongtang uranium deposit in the central Nanling Range is mainly hosted by the Qingzhangshan granite in South China, and was strongly altered by K-feldspar, quartz, chlorite, illite, haematite, pyrite and carbonates. The alteration section can be divided into five horizontal zones: fresh granite (Zone V), a distal alkaline alteration zone (Zone IV), a chlorite-rich zone (Zone III), a close-to-ore sericite/illite alteration zone (Zone II) and a central mineralization zone with strong haematitization (Zone I). Whole-rock geochemistry of the altered samples indicates that from Zone IV to Zone I, the content of SiO2 and U increases significantly. The mass gains of SiO2, MgO and Fe2O3 were proportional to the concentration of U. The content of trace elements (such as Ba, K, La, Ce, Pr, Sr, P, Eu, etc.) gradually decreases from Zone V to Zone I. The rare earth elements manifest a decrease in light rare earth elements and a slight increase in heavy rare earth elements accordingly from Zone V to Zone I. This study shows that the ore materials of the Egongtang deposit were mainly derived from the Qingzhangshan granites. In the early alkali alterations, large amounts of U were partitioned into the fluids. In the ore-forming stage, ores precipitated accompanied by acid metasomatism such as chloritization, haematitization and carbonation.