Undesirable side effects and multidrug tolerance are the main holdbacks to the treatment of cancer in conventional chemotherapy. Fortunately, targeted drug delivery can improve the enrichment of drugs at the target site and reduce toxicity to normal tissues and cells. A targeted drug delivery system is usually composed of a nanocarrier and a targeting component. The targeting component is called a "ligand". Aptamers have high target affinity and specificity, which are identified as attractive and promising ligands. Therefore, aptamers have potential application in the development of smart targeting systems. For instance, aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and epidermal growth factor receptor (EGFR). Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy. This article reviews the application of aptamers as smart ligands for targeted drug delivery in cancer therapy. Special interest is focused on aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery.