We previously reported a novel drug delivery system, drug-linker-Phe-Phe-Arg-methylketone (FFR-mk)-factor VIIa (fVIIa). The method utilizes tissue factor (TF), which is aberrantly and abundantly expressed on many cancer cells. The advantage of this delivery system is its ability to furnish a potent anticancer drug specifically to the tumor vasculature and cancer cells. In this paper, we describe the synthesis of paclitaxel (PTX)-Phe-Phe-Arg-chloromethyl ketone (FFR-ck), followed by coupling with fVIIa to form PTX-FFR-mk-fVIIa. FFRck was separately linked to the OH groups at the C2' or C7 positions of PTX (C2'- or C7-PTX-FFRck), the C2' analogue exhibiting better activity against human head and neck squamous KB 3-1 cells. The activity order against PTX-sensitive KB 3-1 cells is C2'-PTX-FFRmk-fVIIa > PTX > C2'-PTX-FFRck. The C2' complex shows an IC(50) of 12 nM against the PTX-sensitive cell line and 130 nM against PTX-resistant cells.