Chemotherapy is currently one of the most effective ways to treat cancer. However, traditional chemotherapy faces several obstacles to clinical trials, such as poor solubility/stability, non-targeting capability and uncontrollable release of the drugs, greatly limiting their anticancer efficacy and causing severe side effects towards normal tissues. Supramolecular chemotherapy integrating non-covalent interactions and traditional chemotherapy is a highly promising candidate in this regard and can be appropriately used for targeted drug delivery. By taking advantage of supramolecular chemistry, some limitations impeding traditional chemotherapy for clinical applications can be solved effectively. Therefore, we present here a review summarizing the progress of supramolecular chemotherapy in cancer treatment based on host–guest recognition and provide guidance on the design of new targeting supramolecular chemotherapy combining diagnostic and therapeutic functions. Based on a large number of state-of-the-art studies, our review will advance supramolecular chemotherapy on the basis of host–guest recognition and promote translational clinical applications.