Onconase, also called P30 protein, is a member of RNase A superfamily, and is the only enzyme of this class that reached clinical trials. It has weak RNase activity and strong cytotoxicity to various tumor cells in vitro as well as EM>in vivo/EM>, and it is one of the 100 new drugs in research recently. Onconase was first found in early embryos of leopard frog (Rana pipiens), and onconase can trigger apoptosis of tumor cells via degrading RNA, leading to inhibiting sythesis of protein. In addition, onconase has other anticancer mechanisms, such as influencing expression of specific genes and destroying telomerase RNA. Onconase could also enhance the cytotoxicity of other anticancer drugs. The phase I and phase I/II clinical trials of onconase as a single therapeutic agent in patients with non-small cell lung cancer and other solid tumors is conducting, and the phase III human clinical trials for the treatment of unresectable malignant mesothelioma (MM) is undergoing. Onconase may serve as a second-line therapy for MM.