A new generation of nanoparticle carrier that allows efficient delivery and real-time imaging of siRNA in live cells has been developed by combining two distinct types of nanomaterials, semiconductor quantum dots and amphipols. An important finding is that, although amphipols are broadly used for solubilizing and delivering hydrophobic proteins into the lipid bilayers of cell membrane, when combined with nanoparticles, they offer previously undiscovered functionalities, including cytoplasm delivery, siRNA protection, and endosome escape. Compared with the classic siRNA carriers such as Lipofectamine and polyethyleneimine, this new class of nanocarrier works in both serum-free and complete cell culture media, which is advantageous over Lipofectamine. It also outperforms polyethyleneimine in gene silencing under both conditions with significantly reduced toxicity. Furthermore, the intrinsic fluorescence of quantum dots provides a mechanism for real-time imaging of siRNA delivery in live cells. This new multifunctional, compact, and traceable nanocarrier is expected to yield important information on rational design of siRNA carriers and to have widespread applications of siRNA delivery and screening in vitro and in vivo.