Targeted chemotherapy is a novel approach to cancer therapies. This study evaluated the anti-tumor effects of conjugates made by coupling cytotoxic paclitaxel to the somatostatin analog octreotide in A549 human non-small-cell lung cancer (NSCLC) cells xenografted into nude mice. Two cytotoxic somatostatin analogs, paclitaxel-octreotide and 2paclitaxel-octreotide, were prepared by the coupling of one or two paclitaxel molecules with an octreotide molecule. A549 xenografts expressed mRNAs for type 1, 2, 4, and 5 somatostatin receptors. Immunohistology revealed that type 2 somatostatin receptors were mainly located in tumor cell membrane but type 5 somatostatin receptors were found in tumor cell membrane and cytoplasm. Significant tumor growth inhibition was achieved by 2paclitaxel-octreotide at 150 nM/kg and 300 nM/kg. 2paclitaxel-octreotide also significantly extended the tumor doubling time and significantly reduced tumor microvessel density at these doses. Moreover, there was more fragmented DNA in the 2paclitaxel-octreotide single and double dose groups than in the controls. Paclitaxel was ineffective and more toxic than the conjugate as shown by the significant decline of body weight in Paclitaxel group on Days 6, 12, and 26 compared to those treated with 2paclitaxel-octreotide (P<0.05). White blood cell counts in the paclitaxel single and double dose groups were also significantly less than in the controls (P<0.05). In conclusion, the targeting conjugate 2paclitaxel-octreotide made by coupling two molecules of cytotoxic paclitaxel to one somatostatin analog octreotide could enhance tumor growth inhibition and reduce toxicity in comparison to using the cytotoxic paclitaxel alone.