Liver cancer is the fifth most common cause of cancer death among males, and 7th among females. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are both promising treatments for intermediate stage liver cancer, however the treatments are currently administered separately at different procedures This study aimed to develop a biodegradable microsphere loaded with both chemotherapy drug, Doxorubicin (Dox) and radioactive agent, Samarium-153 (153Sm). The microspheres were synthesized using a water-in-oil-in-water solvent evaporation method and then irradiated via neutron activation to produce the radioactive Dox-153Sm-PHBV microspheres. The physiochemical properties, 153Sm radioactivity, Dox loading content, 153Sm retention efficiency, and in-vitro drug release in phosphate buffer solution (PBS) were analyzed. The microspheres cytotoxicity was tested on Hepg2 cell line at 72 h. The microspheres were spherical with a diameter of 24-36 micrometers and a density of 1.438 g/cm3. The specific activity of the Dox-153Sm-PHBV microspheres was 8.68 GBq/g. The microspheres were thermally stable up to 155.23°C and had an encapsulation efficiency of 98.41%. In vitro release studies showed that the microspheres released 65.21% of Dox in PBS solution of pH 7.4, and 29.96% of Dox in PBS solution of pH 5.0 after 984 hours. In vitro cytotoxicity tests showed that the Dox-153Sm-PHBV microspheres were more cytotoxic to HepG2 cells than 153Sm-PHBV or Dox-PHBV microspheres. The Dox-153Sm-PHBV microspheres developed in this study fulfilled all the desirable physicochemical properties for a chemo-radioembolization agent. Further studies are needed to compare the synergistic effect of radio-chemoembolization with the conventional approaches (TACE and TARE).