Immunoliposomes modified by monoclonal antibodies are promising agents for tumor-targeted drug delivery. Here, we designed a novel long-circulating liposome conjugated to a fully human anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) as a targeting modification. VEGF mAb selectively accumulates in tumor tissue over-expressing VEGF; therefore, drugs accumulate within tumors to enhance antitumor efficacy. For this study, paclitaxel (PTX), a chemotherapeutic agent with potent antiangiogenic activity, was used as a prototype drug. PEGylated liposomes loaded with paclitaxel were successfully prepared using the thin-film hydration method with appropriate amounts of S100PC, cholesterol, and mPEG2000-DSPE at a molar ratio of 90:10:5. The VEGF mAb was then conjugated to the Mal-PEG2000-DSPE liposome at a ratio of 6.65mg of VEGF mAb/μmol Mal-PEG2000-DSPE, producing completely stable VEGF mAb-liposomes. The anticancer activity was evaluated in BALB/c nude mice bearing SGC-7901 xenografts. The results indicate that VEGF-targeted mAb-liposomes are visualized in the interior of the tumor and taken up by tumor cells. After receiving five i.v. injections, the mice treated with mAb-liposomal paclitaxel showed superior anticancer activity than the commercial formulation Taxol(®) and unmodified liposomal formulations. Immunohistochemical analysis of the tumor tissues showed weaker VEGF and CD31 signals in mAb-liposome-treated tumors compared to treatment with no mAb-liposomes. Immunohistology analysis results demonstrated that the tumors treated with VEGF mAb-liposomes had the lowest concentration of Ki67-labeled cells and the greatest number of TUNEL-positive cells. All data showed that the novel VEGF mAb-liposomes carried anticancer drugs, such as paclitaxel, to the interior of solid tumors and inhibited tumor growth effectively.