The activation of hepatic stellate cells (HSCs) is an important step in the progress of liver fibrosis. Fibrosis can be impeded by HSC reversion to a quiescent state or HSC clearance through apoptosis. To investigate the apoptotic effects of hsian‐tsao ( Mesona procumbens Hemsl) on human HSCs, the expression levels of cleaved caspase‐3, p38, and c‐Jun N‐terminal kinase (JNK) were assessed using Western blotting, and the caspase‐3 activity was measured using caspase‐3/CPP32 colorimetric assay kit. Hsian‐tsao extract (HTE) increased the activity of caspase‐3 and the level of activated caspase‐3, indicating the activation of apoptosis. The intracellular reactive oxygen species (ROS) level increased in a dose‐dependent manner. This increase was prevented by an antioxidant, suggesting that HTE induces ROS accumulation. In addition, we found that HTE induced the phosphorylation of the mitogen‐activated protein kinases JNK and p38. These collective data indicate that HTE induces apoptosis via ROS production through the p38, JNK, and caspase‐3‐dependent pathways. HTE may decrease HSC activation in liver fibrosis and may have a therapeutic potential.