Background/Aim: Hydrogen sulfide (H<sub>2</sub>S) has been found to act as a physiological intercellular messenger to regulate cell survival. In this study, we evaluated whether H<sub>2</sub>S could promote cell proliferation and melanin synthesis in human epidermal melanocytes (HEMs). Methods: Primary HEMs were cocultured with sodium hydrosulfide (NaHS, the most widely used H<sub>2</sub>S donor) or endogenously overexpressed with cystathionine-γ-lyase (CSE) gene, which is the most predominant H<sub>2</sub>S-producing enzyme. Then, cell viability, intracellular melanin content, tyrosinase (TYR) activity, and expression of microphthalmia-associated transcription factor (MITF), TYR, together with TYR-related protein 1 (TRP-1) in both transcript and protein levels, were detected. Results: We first confirmed that NaHS (10–100 μm) increased cell viability, intracellular melanin content, and TYR activity in a dose-dependent manner. Then, we found that endogenous H<sub>2</sub>S production also promoted cell proliferation, intracellular melanin content, and TYR activity. In addition, we observed the mRNA and protein expression of MITF, TYR, and TRP-1 was significantly up-regulated after NaHS treatment and CSE gene transfection. Conclusions: This study demonstrates that H<sub>2</sub>S promotes cell proliferation and melanin synthesis in HEMs, which indicates pharmacologic regulation of H<sub>2</sub>S may be potential treatment for skin disorders caused by loss of melanocytes or dysfunction of melanogenesis.