Deep geological repository (DGR) has been considered as a globally accepted strategy to dispose high-level radioactive wastes. During long storage periods of 100,000 years, uranium (U) could be migrated through fractures in deep granite aquifers and interact with indigenous bacteria under anaerobic condition. Anaerobic bacteria can reduce U(VI) and further precipitate in the form of U(IV)-oxide minerals by transferring electrons through c-type cytochrome. In this point of view, a comprehensive understanding of uranium-microorganisms interaction is necessary to guarantee the safety of high-level radioactive waste disposal. Although diverse bacterial communities are present in DGR environment, a number of studies have been focused on some model bacteria, such as Desulfovibrio, Geobacter, and Shewanella spp.. In this study, indigenous bacterial community in deep granitic groundwater at 234–244 m was inoculated to sterile uranium-contaminated granitic groundwater amended with 20 mM of sodium acetate, and then incubated under anaerobic condition for 12 weeks. Bio-reduction of U(VI) to U(IV) by indigenous bacteria in uranium-contaminated groundwater was investigated during whole operation period. Initial U(VI) concentration of 885.4 μg·L−1 gradually decreased to 586.1 μg·L−1, resulting in approximately 33.8% of aqueous U(VI) removal efficiency. Oxidation-reduction potential (ORP) value was gradually decreased from 175.4 mV to –243.0 mV after the incubation of 12 weeks. The decrease in ORP value was attributed to the presence of aerobic bacteria and facultative anaerobic bacteria in indigenous bacterial community. The shift in bacterial community structure was observed by 16S rRNA gene high-throughput sequencing analysis. Proteobacteria (55.6%), Firmicutes (24.1%), Actinobacteria (5.5%), and Bacteroidetes (5.4%) were dominant in initial indigenous bacterial community, while Proteobacteria (94.8%) was found to be the only abundant phylum after the reaction. In addition, great increase in the relative abundance of sulfate-reducing bacteria (SRB) was observed: the relative abundance of SRB increased from 11.4% to 44.3% after the reaction. This result indicates that the SRB played a key role in the removal of aqueous U(VI). This finding shows the potential of aqueous U(VI) removal by indigenous bacteria in DGR environment.