Hydrogen sulfide (HS) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. HS-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, HS 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 HS-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of HS in cancer, with an emphasis on the molecular mechanisms by which HS promotes cancer development, progression, dedifferentiation, and metastasis.