Solubility of hydrogen sulfide (H2S) in 46 single and blended physical absorbents, amines, ionic liquids, and hybrid absorbents of amines + ionic liquids and amines + physical absorbents was successfully predicted based on artificial neural networks (ANNs). Three neural network algorithms of Levenberg–Marquardt (LM), Bayesian regularization (BR), and scaled conjugate gradient (SCG) were applied for architecting the ANN models. The results showed that both the number of hidden neurons and the prediction algorithm affected the prediction of H2S solubility. Based on the mean square error (MSE) and determination coefficient (R 2), the most attractive model was the LM-ANN model with 17 hidden neurons. As a result, very satisfactory prediction performance (for the testing data set) with an MSE of 0.0014 and an R 2 of 0.9817 was obtained from the developed LM-ANN model. Additionally, a parity chart confirmed that the predicted solubility of H2S well aligned with the experimental data. To effectively absorb H2S and maintain high solubility of H2S, the absorbent should be well complied with the operating pressure. For a low-pressure range of less than 100 kPa, amines are very attractive. As the pressure elevated to 100–1000 kPa, amines and hybrid amine + physical absorbents are suggested. Lastly, at a high pressure over 1000 kPa, physical absorbents and ionic liquids are recommended.