Cationic multifluorescent quantum dot liposomes (QD-Ls) have been prepared with both hydrophobic and hydrophilic CdSe/ZnS quantum dots by reverse phase evaporation. QD incorporation was confirmed by fluorescence and confocal microscopy. Incorporation did not affect QD photoactivity or damage bilayer or liposome structure. Cell uptake was examined in human hepatocellular carcinoma cells (HuH-7) using cationic and zwitterionic QD-Ls. Cationic QD-Ls were stable in vitro and exhibited high uptake, while zwitterionic QD-Ls aggregated and exhibited low uptake. Given that liposomes are established and versatile platforms for creating cell-targeting therapeutic agents, multifluorescent QD-Ls may offer advanced techniques for imaging hydrophobic and hydrophilic domains simultaneously. If coupled with an encapsulated drug, QD-Ls could be multifunctional and provide imaging, detection, and drug delivery in a single assembly.