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Hydrogen sulfide (H₂S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H₂S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H₂S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia–mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H₂S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H₂S in cancer, with an emphasis on the molecular mechanisms by which H₂S promotes cancer development, progression, dedifferentiation, and metastasis.