The solubility of hydrogen sulfide (H2S) hydrate, which determines the minimum concentration required for hydrate stability, is critical for the production and transportation of natural gas and the safety of H2S emissions. Herein, Raman spectroscopy was used to measure the solubility of H2S hydrate in water at a temperature of 273.15–301.15 K and pressures ranging from the hydrate–liquid–vapor (H–Lw–V) three-phase equilibrium pressure for each temperature to 100 MPa. The results showed that the solubility of H2S hydrate in water increases with temperature under H–Lw–V three-phase equilibrium conditions. Meanwhile, under hydrate–liquid two-phase equilibrium conditions, the solubility increases significantly with temperature at constant pressure but decreases slightly with pressure at constant temperature. The three-phase solubility can be expressed as mH2Smol∙kg-1=exp-6176.6286/T+20.8318, where the temperature is in K, and the two-phase solubility also depends on the pressure in MPa: mH2Smol∙kg-1=exp-21.1-0.0182P-6281.47-4.23P/T. In addition, a thermodynamic model based on the van der Waals-Platteeuw theory was developed to predict the solubility of H2S hydrate in water and the relative deviations of the solubility of H2S hydrate (AADP) demonstrating the model’s capability to accurately predict the H2S hydrate solubility in water.