Aim Hepatocellular carcinoma (HCC) is one of the most heterogeneous cancers worldwide, finding novel validate prognostic biomarker is the aim of this work. Main method Expression of AASS (aminoadipate-semialdehyde synthase) was assayed in three independent cohorts, and the diagnostic and prognostic values of this gene was also evaluated. Clinical indicators significantly associated with AASS were also analyzed. In vivo and in vitro studies were also performed to test the molecular functions of AASS. Finally, the pathways associated with AASS were identified. Key findings AASS was significantly down-regulated in tumor tissues compared to the corresponding normal tissues in three independent datasets, and AUROC (area under receiving operating characteristic curve) were 0.80, 0.87 and 0.77. In addition, the high expression of AASS predicts a better survival in these three datasets. Also, expression of AASS in the metastasis-incline HCC samples (MIH) is significantly lower than the metastasis-averse HCC samples (MAH). Clinical correlation analyses revealed differentiation level, primary tumor diameter and embolus presentation was significantly associated with AASS. Following knock down and overexpression of AASS, the migration and proliferation rate was significantly enhanced. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that AASS was significantly associated with metabolism pathways. Significance Our work identified a valuable biomarker, AASS, for both diagnosis and prognosis, and might be used as a target for HCC therapy.