To investigate whether a series of water-soluble cross-linked chitosan derivates synthesized in the guide of imprinting technology could be used as a uranium chelating agent to protect cells exposed to depleted uranium (DU), the imprinted chitosan derivates with high UO₂²⁺ chelating ability were screened, and cell model of human renal proximal tubule epithelium cells (HK-2) exposed to DU (500 μmol·L⁻¹) was built, chitosan derivates (400 mg·L⁻¹) was added to test group and diethylenetriaminepentaacetic acid (DTPA, 50 mg·L⁻¹) was added to positive control group.  The results showed that three Cu²⁺ imprinted chitosan derivates had higher uranium chelating ability (> 49 μg·mg⁻¹) than chitosan and non-imprinted chitosan derivates.  Compared to the cells exposed to DU only, survival of cells in group added chitosan derivates rose up significantly (increased from 57.3% to 88.7%, and DTPA to 72.6%), and DU intracellular accumulation decreased, membrane damage and DNA damage also eased.  Among the imprinted chitosan derivates, Cu²⁺ imprinted penta dialdehyde cross-linked carboxymethyl chitosan (Cu-P-CMC) was the best, and better than DTPA.  From ultrastructure observation, the DU precipitates of test group added Cu-P-CMC were most grouped in a big hairy clusters in a string together outside cells.  It is possible that the DU-chitosan derivates precipitates are too big to enter into cells, and from this way, the DU uptake by cells decreased so as to detoxication.