The hydroxyapatite (HAp) NPs was synthesized by co-precipitation method and Al2O3 shell was coated by sonochemical process. Gelatine(GEL) and folic acid(FA) are attached onto the nanoparticles utilizing different techniques. HAp@Al2O3-gelatin-folic acid (HAp@Al2O3-GEL-FA) core-shell nanostructures were characterized by FTIR, XRD, and HR-TEM techniques. The incorporation of gelatin-folic acid onto HAp@Al2O3 NPs exhibited good water dispersibility, enhanced drug delivery efficiency, and remarkable targeting ability to cancer cells. 5-fluorouracil (5-Flu) was used as a model drug. The in-vitro drug release of HAp@Al2O3-gelatin-folic acid NPs was studied at different pH conditions (7.4 and 6.3). Cytotoxicity of free HAp@Al2O3-GEL-FA NPs, free 5-Flu, and 5-Flu loaded former NPs was investigated against ovarian cancer cell line (SKOV3). The results shown that the 5-Flu loaded HAp@Al2O3-gelatin-folic acid NPs show greater cytotoxicity due to the folate receptor- over expressing in cancer cells. The present findings show that 5-Flu loaded gelatin-folic acid incorporated HAp@Al2O3 core-shell nanoparticles are promising for receptor-mediated targeted drug delivery system.