Abstract: Objective: To explore the potential role of nitidine chloride(NC)targeting the expression of potential target gene the establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2)in hepatocellular carcinoma(HCC).Methods: The expression of ESCO2 in HCC and its clinical significance were studied at tissue levels.Based on The Cancer Genome Atlas (TCGA) database, the relationship between the expression of ESCO2 and clinical parameters and prognosis of patients with HCC was analyzed.Based on the identified ESCO2 differentially coexpressed genes (DCGs), the potential signal pathways were predicted, and the protein-protein interaction network(PPI)was drawn.In addition, the effect of NC on ESCO2 in HCC was studied by using nude mouse HCC models and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).Results: Microarray and high-throughput sequencing analysis showed that ESCO2 was highly expressed in HCC compared with normal liver tissues (SMD=0.90, I²=92.0%, P＜0.001).The high ESCO2 expression was correlated with patients'age, tumour grade, T stage, and pathological stage.High expression of ESCO2 was associated with a poor prognosis of HCC (P＜0.01).Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the most important enrichment pathway was the cell cycle. In vivo and in vitro experiments showed that ESCO2 was significantly down-regulated in NC-treated nude mouse HCC models and SK-HEP-1 cells(P＜0.01).Conclusion: High expression of ESCO2 plays a cancer-promoting role in HCC, and ESCO2 may be a potential target for NC treatment of HCC patients.