Hepatocellular carcinoma(HCC) is the world's most common cause of cancer death. Therefore, more molecular mechanisms need to be clarified to meet the urgent need to develop new detection and treatment strategies. We selected three liver cancer transcriptome database GSE124535, GSE136247, GSE144269, and analyze the overexpressed genes contained in them. The overlapping genes were found by Venn map, and two interacting networks module, were found by Mcode. Module1 is mainly related to mitosis and cell cycle, and module2 is mainly related to EMT, angiogenesis, glycolysis and so on. We found that the seed gene in module2 is VCAN. The purpose of this study is to study the expression characteristics of VCAN gene in HCC, and to explore its role in the occurrence and development of HCC and its possible mechanism. Data from TCGAportal shows that compared with normal tissues, the expression of VCAN is up-regulated in HCC tissues. The patients with high expression of VCAN had shorter distant recurrence-free survival and overall survival. The effects of VCAN expression on cell proliferation, invasion and migration were evaluated in vitro by using gene knockout and overexpression strategies. Multiple possible VCAN interactions have also been identified. These result reveal that the level of VCAN is higher in the subtypes of HCC with higher malignant degree and is connected to the poor prognosis. In addition, the treatment of VCAN with DNA methyltransferase inhibitors and transcription factor inhibitors may improve prognosis of patients with liver cancer.