In the current study, using arg-ii−/− as well as the arg-ii-overexpressing melanoma and lung carcinoma cells, we demonstrate a critical role of Arg-II-Sirt3-mtROS cascade in promoting tumour cell growth, migration, nuclear deformation and DNA damage linking to progression and malignancy of melanoma as well as of lung cancer cells, which could be the therapeutic targets for treatment the cancers. The gene discussed is SIRT3; the disease is melanoma.