Background As a neuromodulator, hydrogen sulfide （H2S） participates in various pathophysiological events in mammalian body, such as the regulation of synaptic activity, facilitating effect of long-term potentiation, and participation in pain responses. Now many researchers increasingly focus on pain modulation of H2S. Objective This review is to sum the research progress in pain modulation of H2S. Content It is elaborated in the following aspects: the biological properties of H2S, the potential mechanisms by which how the H2S is involved in pain, and the roles the H2S played in different types of pain. Trend H2S, a novel nociceptive messenger in mammalian body, plays a critical roles in the development of pain. Better understanding of the physiological role of H2S and further clarifying the specific mechanisms by which the H2S is involved in pain can provide a new strategy for the clinical treatment of pain.