Herein, MOF-808 (MOF = metal-organic framework) based on zirconium tricarboxylate was synthesized to investigate the influence of decorating groups of folic acid-conjugated chitosan (CS-FA) on drug-delivery efficiency. Quercetin (QU) was loaded on nondecorated MOF-808 and then decorated with a folic acid-chitosan conjugate. The properties and activities of modified MOF-808 were compared with unmodified MOF-808. QU@MOF-808@CS-FA exhibited favorable drug-release properties, high drug-loading capacity, efficient targeting capability, and pH-dependent release behavior, highlighting the critical role of organic modification. A variety of characterization techniques were used to characterize MOF nanoparticles, including Fourier transform infrared, powder X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray, transmission electron microscopy, Brunauer-Emmett-Teller, ζ potential, and 1H NMR. Additionally, Monte Carlo simulation calculations were carried out to examine the interactions between the structures of MOF-808 and QU. An in vitro cytotoxicity test was conducted, and the results identified that QU@MOF-808@CS-FA demonstrated more superior therapeutics than QU@MOF-808 on FR-positive MCF7 cancerous cells. On the basis of the results, QU@MOF-808@CS-FA is a promising drug carrier by selective targeting and sustained release.