Alliin is an important organosulfur compound derived from garlic. In this study, the role of alliin in myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms were investigated. Treatment with alliin significantly reduced the area at risk and the infarct area in a mouse model of I/R injury. Besides, compared with I/R group, the cardiac function was significantly improved in I/R + alliin group. Treatment with alliin attenuated hypoxia/reoxygenation (H/R) induced apoptosis of cardiomyocytes. The results of the following high throughput RNA-sequencing revealed that autophagy participates in the myocardial protection role of alliin. Treatment with alliin decreased apoptosis and increased the autophagy activity in vivo. Autophagic flux in primary mouse cardiomyocytes was monitored using mRFP-GFP-LC3 adenovirus, and the results indicated that alliin could increase the autophagic flux. Moreover, the myocardial protective effect of alliin could be reversed by administration of autophagy inhibitor 3-MA. In conclusion, all the results indicated that alliin alleviates myocardial ischemia-reperfusion injury by promoting autophagy. (C) 2019 Elsevier Inc. All rights reserved.