Background: Transarterial radioembolization (TARE) represents an effective targeted therapeutic option for hepatocellular carcinoma (HCC), a cancer with high mortality and poor prognosis. The aim of this study was the preparation and preliminary biological evaluation of 177Lu-labeled polyhydroxamic acid (PHA) microparticles toward possible use in the therapy of HCC. Materials and Methods: PHA microparticles were synthesized starting from polyacrylamide. They were characterized by Fourier-transform infrared spectroscopy (FT-IR), visual color test, and laser diffraction particle size analysis. Experimental variables such as reaction pH, amount of PHA microparticles, carrier Lu content, and incubation time were optimized for maximum uptake of 177Lu on PHA microparticles. Stability of 177Lu-PHA microparticles was tested in the presence of competing Fe(III) ions in solution. In vitro stability of 177Lu-PHA microparticles was evaluated in 0.05 M sodium phosphate solution (pH 7.5), saline, and serum. Bioevaluation studies were performed in normal Wistar rats by intrahepatic artery injection of the 177Lu-PHA microparticles. Results: Successful synthesis of PHA microparticles could be confirmed from the results of FT-IR analysis and visual color test. Laser diffraction-based particle size analysis confirmed median particle size to be 54 μm, suitable for TARE. Under the optimized conditions, >99% loading of 177Lu on PHA microparticles could be achieved. Even in the presence of high concentration of Fe(III) ions, 177Lu binding to PHA microparticles was stable. 177Lu-PHA microparticles exhibited excellent in vitro stability in sodium phosphate solution, saline, and serum up to 5 d at 37°C. In the bioevaluation studies performed in normal Wistar rats, 92.8% ± 3.1% of 177Lu-PHA microparticles were retained in the liver at 96 h postinjection without any significant leakage to other organs. Conclusion: This preliminary study demonstrates the potential of synthesized PHA microparticles as carriers of therapeutic radioisotopes such as 177Lu for treatment of HCC.