Abstract: The objective was to investigate the influencing factors on the siRNA delivery efficiency of hydrophobic modified hyaluronic acid with molecular weight 9 600 grafted with spermine and laurylamine cationic micelles(HAPL₉₆₀₀).The transfection efficiency of HAPL₉₆₀₀/siRNA was determined by flow cytometry.The influence of the molecular weight of HA，complexes forming time，the concentration of the HAPL₉₆₀₀，pH，the transfection medium and the weight ratio of HAPL₉₆₀₀ to siRNA on transfection were investigated.The competitive inhibition experiment was studied to investigate the in vivo cell target ability.The results indicated that HAPL₉₆₀₀ would reach the optimal transfection efficiency when the molecular weight of HA is 9 600 with 30 min of complexes forming time,15 mg/mL of concentration of the HAPL₉₆₀₀，8 of the weight ratio of HAPL₉₆₀₀ to siRNA at PBS(pH 6.8) transfection medium.The transfection efficiency of the HAPL₉₆₀₀ was reduced by competitive binding of free HA onto the CD₄₄ receptors，thereby lowering the extent of cellular uptake via CD₄₄ receptor mediated endocytosis，which suggested its in vitro targeting ability on the tumor cells.In all，HAPL₉₆₀₀ could obtain optimal，reduplicate and targeting transfection results by controlling related factors.