Abstract: Hydrogen has been found to be a promising therapeutic gas molecule due to its inherent high biological safety and obvious therapeutic effects on many diseases, though its mechanism is still not very clear. At present, the effect of hydrogen therapy is limited due to the fact that hydrogen molecule through conventional oral administration and bathing cannot accumulate with high concentration in the lesion site because of its non-targeted accumulation and easy diffusion properties. Nanomaterials provide an important way to realize the targeted and controlled delivery of hydrogen. Based on the issue, this review summarizes the targeted controllable hydrogen releasing nanomaterials and the possible mechanisms of hydrogen therapy of different types of diseases. Some opinions and solutions are proposed aiming at the current issues in order to provide guidance and reference for the researches on the mechanism and application of hydrogen therapy.