Hydrogen sulfide (HS) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on HS has been increasing. HS is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of HS in a variety of physiological processes. Current studies have shown that HS is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving HS on physiological and pathological processes, looking forward to providing guidance for subsequent research.