Hepatocyte apoptosis is frequently observed in alcohol‐related liver disease (ARLD), which ranks among the 30 leading causes of death worldwide. In the current study, we explored the impact of S‐allyl‐l‐cysteine (SAC), an organosulfur component of garlic, on hepatocyte apoptosis induced by alcohol. Rat liver (BRL‐3A) cells were challenged by ethanol with or without SAC treatment. Cell death/viability, reactive oxygen species (ROS) generation, mitochondrial Cytochrome C release, and caspase 3 activity were then examined. We found that ethanol remarkably induced apoptosis of hepatocytes, while SAC treatment rescued ethanol‐induced hepatocyte injury, as demonstrated by cell counting kit‐8 (CCK8) assay, TUNEL assay, and annexin V/PI staining assay. Ethanol evoked ROS generation in BRL‐3A cells, and this was abated by SAC pretreatment, as indicated by 2′,7′‐dichlorofluorescin diacetate (DCFDA) staining assay. Moreover, ethanol suppressed cellular anti‐apoptotic protein B‐cell lymphoma‐2 (Bcl‐2) expression, increased pro‐apoptotic protein Bcl‐2‐associated X protein (Bax) expression, induced mitochondrial Cytochrome C release, and activated the caspase 3‐dependent apoptosis pathway in BRL‐3A cells. SAC was sufficient to abolish all these changes induced by ethanol, thereby revealing the molecular mechanisms underlying its protective effects. In conclusion, SAC protects hepatocytes from ethanol‐induced apoptosis and may be suitable for use as a novel anti‐apoptotic agent for treating ARLD.