In human colon cancer cells HCT116 and HT29, xCT is highly expressed, and CES‐derived H2S S‐sulfhydrates OTU domain‐containing ubiquitin aldehyde‐binding protein 1 (OTUB1) at Cys91 to regulate its binding to xCT. The gene discussed is SLC7A11; the disease is colonic neoplasm.