jats:titleAbstract</jats:title>jats:pLow atomicity clusters present properties dependent on the size, due to the quantum confinement, with well‐defined electronic structures and high stability. Here it is shown that Agjats:sub5</jats:sub> clusters catalyze the complete oxidation of sulfur to Sjats:sup+6</jats:sup>. Agjats:sub5</jats:sub> catalytic activity increases with different oxidant species in the order Ojats:sub2</jats:sub> ≪ Hjats:sub2</jats:sub>Ojats:sub2</jats:sub> jats:bold<</jats:bold> OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Agjats:sub5</jats:sub> catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASjats:supG12V</jats:sup>) or through ARID1A mutation, sensitizes cells to Agjats:sub5</jats:sub> mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Agjats:sub5</jats:sub> has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Agjats:sub5</jats:sub> may lead to new redox‐based approaches to cancer therapy.</jats:p>