Activities of CD4⁺ regulatory (T_REG) cells restore immune homeostasis during chronic inflammatory disorders. Roles for T_REG cells in inflammation‐associated cancers, however, are paradoxical. It is widely believed that T_REG function in cancer mainly to suppress protective anticancer responses. However, we demonstrate here that T_REG cells also function to reduce cancer risk throughout the body by efficiently downregulating inflammation arising from the gastrointestinal (GI) tract. Building on a “hygiene hypothesis” model in which GI infections lead to changes in T_REG that reduce immune‐mediated diseases, here we show that gut bacteria‐triggered T_REG may function to inhibit cancer even in extraintestinal sites. Ability of bacteria‐stimulated T_REG to suppress cancer depends on interleukin (IL)‐10, which serves to maintain immune homeostasis within bowel and support a protective antiinflammatory T_REG phenotype. However, under proinflammatory conditions, T_REG may fail to provide antiinflammatory protection and instead contribute to a T helper (Th)‐17‐driven procarcinogenic process; a cancer state that is reversible by downregulation of inflammation. Consequently, hygienic individuals with a weakened IL‐10 and T_REG‐mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated IL‐6 and IL‐17 and show more frequent inflammation‐associated cancers. Taken together, these data unify seemingly divergent disease processes such as autoimmunity and cancer and help explain the paradox of T_REG and inflammation in cancer. Enhancing protective T_REG functions may promote healthful longevity and significantly reduce risk of cancer.