Onconase (ranpirnase) is a homologous protein obtained from Rana pipiens frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease(RN-ase) activity. Onconase induces cell death through the decomposition of inner cellular RNA,inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC).