One difficult issue that environmental scientists are facing is how to convert soluble U(VI) into insoluble U(IV) and recycle it. In the present study, a method, which was widely reported in the literature, was used to collect soluble U(VI) using general biomass (including bacteria and yeast extract), and then a strategy was developed to transform the amorphous uranium-containing precipitates (Uranium–Phosphorus Amorphous Compound, UPAC) into large-sized insoluble UO₂ nanoparticles. The results show that the biomass could precipitate more than 90% of the U(VI) (0.42 mmol L⁻¹) within 10 min. The maximum precipitation capacity of the biomass (dry weight) ranged from 120 to 187 mg U g⁻¹. The UPAC can be further converted into soluble uranyl phosphate compounds (HUO₂PO₄) at room temperature for 90 days or under the hydrothermal condition at 150 °C for 48 h. However, once the hydrothermal temperature was raised to 240 °C, insoluble UO₂ nanoparticles of around 10 nm could be obtained within 48 h. This work provides a new possibility for the cost-effective preparation of nuclear fuel (UO₂) with inexpensive raw materials. The mechanism correlating to the transformation of the UPAC into inorganic UO₂ is also discussed here.