MicroRNAs (miRNAs) are the short endogenous non-coding RNAs that regulate the expression of the target gene at posttranscriptional level through degrading or inhibiting the specific target messenger RNAs (mRNAs). MiRNAs regulate the expression of approximately one-third of protein coding genes, and in most cases inhibit gene expression. MiRNAs have been reported to regulate various biological processes, such as cell proliferation, apoptosis and differentiation. Therefore, miRNAs participate in multiple diseases, including ischemia-reperfusion (I/R) injury. Hydrogen sulfide (H 2 S) was once considered as a colorless, toxic and harmful gas with foul smelling. However, in recent years, it has been discovered that it is the third gas signaling molecule after carbon monoxide (CO) and nitric oxide (NO), with multiple important biological functions. Increasing evidence indicates that H 2 S plays a vital role in I/R injury through regulating miRNA, however, the mechanism has not been fully understood. In this review, we summarized the current knowledge about the role of H 2 S in I/R injury by regulating miRNAs, and analyzed its mechanism in detail.