Drug delivery systems offer the advantage of sustained targeted release with minimal side effect. In the present study, the therapeutic efficacy of a porous silica-calcium phosphate nanocomposite (SCPC) as a new delivery system for 5-Fluorouracil (5-FU) was evaluated in vitro and in vivo. In vitro studies showed that two formulations; SCPC50/5-FU and SCPC75/5-FU hybrids were very cytotoxic for 4T1 mammary tumor cells. In contrast, control SCPCs without drug did not show any measurable toxic effect. Release kinetics studies showed that SCPC75/5-FU hybrid provided a burst release of 5-FU in the first 24 h followed by a sustained release of a therapeutic dose (30.7 microg/day) of the drug for up to 32 days. Moreover, subcutaneous implantation of SCPC75/5-FU hybrid disk in an immunocompetent murine model of breast cancer stopped 4T1 tumor growth. Blood analyses showed comparable concentrations of Ca, P and Si in animals implanted with or without SCPC75 disks. These results strongly suggest that SCPC/5-FU hybrids can provide an effective treatment for solid tumors with minimal side effects.