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This study investigates the efficacy of cold atmospheric plasma (CAP) in treating squamous cell carcinoma (SCC), a highly metastatic cancer. To assess the anticancer activity, two CAP treatment methods—direct treatment and indirect treatment (plasma‐treated N‐acetyl cysteine solution)—were used. Results indicate that both methods selectively target SCC cells, inducing oxidative and nitrosative stress, leading to decreased metabolic activity and increased apoptosis. Furthermore, a critical feature of cancer cells, metastatic behavior is also inhibited by CAP treatment. Coculture experiments demonstrate the effectiveness of CAP treatment in selectively inactivating SCC cells while leaving healthy cells unaffected. These findings suggest the potential use of CAP as a selective and effective treatment for SCC. [ABSTRACT FROM AUTHOR]