Polymer nanoparticles have emerged as a promising new strategy for the efficient delivery of drugs. They have several advantages when used as drug carriers, such as high stability, high capacity, improvement of drug bioavailability, as well as allowing for sustained drug release. Quercetin has therapeutic potential as an anticancer drug, but has poor solubility and low bioavailability. In this study it is shown that co-encapsulation of quercetin and fluorescent Silicon quantum dots (SiQDs) in poly (ethylene glycol)-block-polylactide (PEG–PLA) nanoparticles can be used for simultaneous in vitro imaging and to improve the biocompatibility of quercetin. Fluorescent imaging with SiQDs can provide a new concept to monitor the delivery of anti-cancer drugs. The nanoparticles are synthesized based on the double emulsion method and are extensively characterized and assayed for cytotoxicity in vitro. HepG2 cells are incubated with quercetin and SiQDs dual-loaded PEG–PLA nanoparticles, resulting in a red fluorescent staining which can be detected with a confocal microscope. PEG–PLA nanoparticle encapsulated quercetin suppresses human hepatoma HepG2 cell proliferation more effectively than the free-standing form. In addition, nanoparticle-encapsulated quercetin significantly inhibits hydrogen peroxide-induced DNA damage in HepG2 cells. These data show that nanocapsulated quercetin possesses the potential bioactivity to reduce the drug dosage frequency, as well as increase patient compliance. The combination of polymeric nanoparticles and semiconductor quantum dots can allow monitoring of delivery, improve aqueous solubility, and enhance biocompatibility. Such nanoparticulated systems could shape the future of drug delivery.