BACKGROUND: Prussian blue nanoparticles (PBNPs) due to their high solubility, stability, flexible molecular structure, tunable size, easy synthesis, and surface modification have attracted the attention of researchers as high-efficiency therapeutic agents. Recently, it has been reported that magnetic nanoparticles can be to bind pathogenic substances on their surface, followed by a recollection by magnetic separation. Considering the potential application of PB and magnetic nanoparticles, in the current study we aimed to strategically design and synthesize a highly efficient nano-magnetic bilirubin scavenger system based on iron oxides@prussian blue nanocomposites (Fe3O4@PB) NCs. MATERIALS AND METHODS: The Fe3O4@PB NCs were synthesized by an improved shell-growing procedure and identified using advanced characteristic techniques TEM, SEM, XRD, DLS, and Zeta potential. Synthesized Fe3O4@PB NCs showed good magneton properties and also demonstrated dramatic absorbent properties that empower use as an eco-friendly adsorbent nano agent for the detoxification of toxins. In addition, Fe3O4@PB nanoparticles showed high performance of bilirubin absorption in the serum and blood of sickle cell anemia patients. (Temp. 37.7 ºC, the dose of adsorbent: 1 mg/mL, incubation time 30 min, and initial concentration: 0.25 mg/mL). RESULTS: The results demonstrated an ideal adsorption capacity (86%) of Fe3O4@PB NCs which is significant compared to the reported adsorbents agents. These results pave the way for the application of Fe3O4@PB NCs for the effective purification of toxins from patients' body fluids.