Since the discovery of apoptosis signal‐regulated kinase 1 (ASK1), the signal transduction mechanism and pathophysiological process involved in its regulation have been continuously revealed. Many previous studies have identified that ASK1 is involved and plays a critical role in the development of diseases affecting the nervous, cardiac, renal, and other systems. As a mitogen‐activated protein kinase (MAPK) kinase kinase, ASK1 mediates apoptosis, necrosis, inflammation, and other pathological processes by activating its downstream c‐Jun N‐terminal kinase (JNK)/p38 MAPK. Owing to the important role of ASK1, an increasing number of studies in recent years have focused on its status in liver‐related diseases. In this paper, we review the mechanisms and targets of ASK1 in liver‐related diseases to emphasize its important role in the development of liver disease.