Lipoplexes containing a hyaluronic acid-dioleoylphosphatidylethanolamine (HA-DOPE) conjugate were designed to target the CD44 receptor on breast cancer cells. Cationic liposomes composed of a mixture of [2-(2,3-didodecyloxypropyl)hydroxyethyl]ammonium bromide (DE) and dioleoylphosphatidylethanolamine (DOPE) with or without HA-DOPE were prepared, characterized, and used to form a complex with plasmid DNA pCMV-luc. Lipoplexes displayed a negative zeta potential and a mean diameter between 250-300 nm. Cytotoxicity and transfection efficiency of the lipoplexes were determined on the MDA-MB-231and MCF-7 breast cancer cell lines. Cytotoxicity was not modified by the presence of HA-DOPE. However HA-DOPE increased the level of transfection on CD44-expressing MDA-MB-231 cells compared to the MCF-7 line, which expresses very low levels of CD44. The transfection on the MDA-MB-231 cells was highly inhibited by anti-CD44 Hermes-1 antibody but not by the nonspecific anti-ErbB2 antibody. In conclusion, cationic liposomes containing the HA-DOPE conjugate mediated good transfection on CD44 expressing cell lines in culture.