Background: Acyl-coenzyme A cholesterol acyltransferase (ACAT) is a membrane-binding enzyme, which localizes in the endoplasmic reticulum. ACAT2 can promote the progression of colon cancer, but its efficacy in lung adenocarcinoma(LUAD) is still not sure. Method: ACAT2 expression analysis was performed by TIMER2.0 database. GEPIA database was utilized to analyse co-relations between expression of ACAT2 and pathological stage of tumor. Kaplan-Meier analysis was analyzed its potential in clinical prognosis. CancerSEA database analysed correlations between expression of ACAT2 and functional status of different tumor displayed as a heatmap. The molecule interaction network analysis performed by the STRING tool. Results: ACAT2 was upregulated in patients with LUAD, and high expression of ACAT2 had a poor DFS and OS. Cox regression analysis indicated that the poor outcomes might be related to the tumour stage, nodal stage, distant metastatic stage. ACAT2 participated in biological process of cell cycle, DNA repair, DNA damage, proliferation. Enrichment pathway analysis showed four ACAT2-correlated genes, ACOX1, EHHADH, OXCT1, DLAT. Conclusion: ACAT2 might be a novel predictive biomarker and treated target.