APN is an important zinc dependent metallo-exopeptidase, which can degrade the extracellular matrix, and plays an important role in tumor invasion, metastasis and angiogenesis. it has been considered as a suitable target for anti-cancer drug design. Recently, research of structure-based APN inhibitors is becoming an interesting field, and many APN inhibitors have been reported. Here we review a series of APN inhibitors and the recent progress in this field.