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Melanoma is a common malignant skin tumor with highly invasive features and a high metastasis rate that can be difficult to treat clinically. Large-scale resection of primary cutaneous melanoma is often used to avoid postoperative recurrence. For advanced patients, radiotherapy, targeted therapy and immunotherapy are often needed. Low-temperature plasma has been proved to have significant antitumor effects on a variety of cancer cell lines cultured in vitro. The main limitation of direct low-temperature plasma treatment is that it has weak penetration ability and can only treat superficial lesions. In recent years, research on low-temperature plasma-activated solution has revealed that it also have good antitumor effects and low-temperature plasma penetration depth problems can be solved by local injection. The present study revealed that low-temperature plasma-activated phosphate buffer solution exhibited good antitumor effects and biosafety against melanoma in vitro and in vivo. It demonstrated that low-temperature plasma-activated solution has antitumor effects due to its regulation of intracellular redox, destruction of mitochondrial function and DNA damage. In vivo experiments demonstrated that treatment with low-temperature plasma-activated solution not only exhibited antitumor effects but also caused no significant damage to hematopoietic function or liver and kidney functions in mice. All these results demonstrated that low-temperature plasma-activated solution represent a promising antitumor treatment strategy. [ABSTRACT FROM AUTHOR]