Hydroxyapatite (HA) nanostructures have attracted attention due to their great biocompatibility, bioactivity, osteoconductivity and good adherence to bone tissues and osteosarcoma cells, making possible the therapeutic replacement and reconstruction of bone matrix after tumor treatment. However, suitable surface modification is essential to enable the final performance of these materials. This paper describes the synthesis of HA nanorods and a route of functionalization of the HA surface with folic acid (folate). The samples were characterized by XRD, FTIR, TGA, CHN, XPS, BET, SEM and TEM in order to estimate the physical–chemical properties of the nanoparticles, such as morphology, size distribution, pore and surface parameters, and the stability of hydroxyapatite and folate interactions was systematically evaluated. In addition, an in vitro preliminary assay was conducted in order to investigate the biocompatibility of these systems in fibroblast cells. The results indicate that mesoporous hydroxyapatite nanorods around 70 nm were successfully synthesized with pure crystalline phase and folate can be strongly linked to hydroxyapatite nanorod surfaces following the methodology proposed in this work. In addition, this material shows great biocompatibility, presenting cell proliferation as an intrinsic characteristic, making this system suitable for the suggested biomedical applications.