Genistein doped mannoseconjugated PEGmodified liposomes (manPEG@LP/Ge) were prepared via filmsonic method by using targeted lipid DSPEPEGman and helper lipid DOTAP. Concanavalin A (ConA) agglutination assay had proved that mannose has been modified to nanoliposomes successfully. The asprepared manPEG@LP/Ge were spherical in shape with a homogeneous size distribution around (270±15) nm in diameter as characterized by SEM. The Zeta potential was +7.5 mV in pure water. Furthermore, manPEG@LP/Ge appeared to be very homogeneous and stable in water. It is considered that the sterichinerance effects of surface PEG long chain and the strong electrostatic repulsion of the positive charge play an important role in the good dispersion of manPEG@LP/Ge. Flow cytometry examination confirmed the targeting specificity of manPEG@LP/Ge against human hepatoma Huh7 cells which are of overexpression of mannose receptors. The cell toxicity viability demonstrated that unloaded manPEG@LP are practically nontoxic, indicating that the drug delivery vehicles possess excellent biocompatibility. Systematic in vitro and in vivo studies showed that the manPEG@LP/Ge kill tumor cells with high specificity and excellent efficiency, owing to the mannosemediated active tumortargeted drug delivery.