Abstract. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, yet effective treatment for this disease is lacking. Thus, there is an urgent need to identify novel therapeutic targets for this dreadful disease. Numerous studies have established that overexpression of astrocyteelevated gene-1 (AEG-1) is frequently observed in multiple types of cancers including HCC, and its expression levels are correlated with the stage and grade of the disease. Further studies revealed that AEG-1 plays a key role in several crucial aspects of HCC progression, including growth, transformation, cell survival, invasion, metastasis and chemoresistance. Moreover, AEG-1 overexpression activates the Wnt/β-catenin, mitogen-actived protein kinase (MAPK), nuclear factor (NF)-κB, and PI3K/Akt signaling pathways, and promotes its downstream gene expression to facilitate malignant potential. Recently, transgenic mice with hepatocyte-specific expression of AEG-1 (Alb/AEG-1) and AEG-1-knockout mouse both revealed novel aspects of the functions of AEG-1 in an in vivo context. This review evaluates the multi-functions of AEG-1 and describes the major signaling pathways and molecular alterations regulated by AEG-1 in HCC, indicating its key roles and potential as a biomarker or significant target for the therapy of HCC.