Cancer cells can develop in several ways to escape from death induced by chemotherapeutic agents, thereby weakening the anti-tumor efficacy of single-target chemotherapy. Therefore, the efficacy of conventional chemotherapy hits a single target in tumor cells subject to strict limits. In this article, an AS1411 aptamer-functionalized liposome is prepared, which can simultaneously deliver paclitaxel (PTX) and siRNA into MCF-7 cells in vitro and in vivo. The simultaneous delivery of PTX and siRNA synergistically increased the number of apoptotic cells and reduced angiogenesis. This delivery method exhibited significant advantages over combined delivery of PTX and siRNA separately by different liposomal drug delivery systems. Therefore, the simultaneous delivery of PTX and PLK1-targeted siRNA using AS1411 aptamer-functionalized liposome may have good potential clinical value for the therapy of breast cancer. Nanomedicine based on simultaneous delivery of chemotherapy drugs and siRNA gene provides an effective platform for improving tumor treatment methods.