Chemotherapy is one of the most important treatment modalities for liver cancer, especially for those who are judged as being unsuitable for surgical resection, local ablative therapy, or transarterial chemoembolization. However, the efficacy of chemotherapy is still unsatisfactory due to the long duration, side effects and the tendency to develop drug resistance. The development of novel anti-liver cancer drugs remains imperative. Cyclopeptides have been recognized as new chemical modalities in drug design due to their unique constrained structures, extensive biological activities, higher metabolic stability, cell permeability and bioavailability than linear peptides. A lot of cyclic peptides have been found with potential anti-proliferative activity against malignant cells, and many of them showed excellent anti-liver cancer activity. In this review, we will discuss in detail the structures and the anti-liver cancer activity of small and medium-sized cyclopeptides, aiming to offer some elicitation to chemotherapeutic drug design based on cyclopeptides.