Folic acid (FA)-functionalized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles were prepared to enhance the delivery efficiency of the anticancer drug etoposide for the clinical treatment of osteosarcoma. PHBV nanoparticles were synthesized by emulsification/solvent evaporation technique and obtained in the size range of 200-250 nm and zeta potential range of -21 and -27 mV. Encapsulation efficiency and in vitro drug release were studied. The cytotoxic, apoptotic, and necrotic effects of PHBV nanoparticles were also investigated using Saos-2 osteosarcoma cells. The results obtained in this study demonstrate that etoposide-loaded and FA-functionalized PHBV nanoparticles can be successfully used for targeted treatment of osteosarcoma.