With the increasing demand for uranium in the nuclear industry, the unintended uranium contamination of skin or clothing for individuals involved in nuclear activities has raised public health concerns. Herein, a plant polyphenol-based surfactant (sulfonated bayberry tannin surfactant, SBTS) was fabricated by modifying the hydrophobic groups in the sulfonated bayberry tannin (SBT) structure using a simple Friedel–Crafts alkylation reaction. The surfactant modified with tetradecane chloride showed superior foaming ability and emulsifying properties compared with SBT. The characterization of SBTS by FT-IR spectroscopy confirmed that hydrophobic chains were successfully grafted on SBT molecules via covalent bonds. As expected, SBTS could disperse in water under near-neutral pH condition, and showed good foaming and emulsifying properties. Moreover, the surfactant exhibited effective removal ability for UO22+-contaminated cotton fabric and skin in a broad application range, reaching a removal rate of 99 % for low amounts of UO22+, and even above 55 % for high UO22+ amounts. More importantly, SBTS could be easily separated from aqueous systems after standing for 60 min in acidic and neutral conditions, which is a favorable feature to avoid secondary pollution. In vitro cytotoxicity tests suggested that SBTS was much safer than commonly used synthetic surfactants. Based on XPS and FT-IR measurements, we propose a decontamination mechanism mainly originating from the chelation effect between the phenolic hydroxyl group of SBTS and UO22+. This study highlights the potential of plant tannin surfactants as effective materials for the removal of UO22+ from skin or clothing of individuals involved in various nuclear-related activities.