Abstract: This study aimed to analyze gene function of cysteinyl aspartate specific proteinase-1（caspase-1, CASP1） gene in hepatocellular carcinoma（HCC） based on bioinformatics analyses and the effect of CASP1 knockdown on liver cancer cells. CASP1 expression in human HCC tissues and the relationship between CASP1 and overall survival（OS） of liver cancer patients were analyzed by UALCAN, the Human Protein Atlas and LinkedOmics databases. The GO and KEGG enrichment analyses were conducted for the co-expression gene set of CASP1. The CASP1 gene was knocked down by CRISPR/Cas9 system in the HepG2 cell. Sequencing, RT-PCR and western blotting were used to confirm the knockdown. The CCK-8 assay, transwell assay and Annexin V-FITC/PI double-stained assay were employed to detect the effect of CASP1 knockdown on cell proliferation, cell invasion and cell apoptosis of HepG2 cells. The results showed that CASP1 mRNA expression levels were significantly higher in tissues from HCC patients with TP53 gene mutation（P＜0.01）, compared with normal tissues and those of patients without TP53 gene mutations. HCC patients with high expression of CASP1 had a significantly reduced OS（P=0.033）. High CASP1 expression was further associated with a reduced OS among patients in clinical stage Ⅰ and stage Ⅱ（P=0.023 2）. There was no significant difference in OS according to CASP1 expression among patients in clinical stage Ⅲ and stage Ⅳ（P=0.471 3）. The enrichment analyses of the co-expression gene set of CASP1 showed that they were associated with immune responses（especially for innate immune responses mediated by NK cells and phagocytes, and adaptive immune responses mediated by T cells）. After the CASP1 gene was knocked down, the proliferative ability of cells increased, the invasion abi-lity of cells was enhanced and decreased apoptosis occurred in HepG2 cell. In summary, CASP1 has both oncogenic and tumor suppressor functions in HCC. Downregulation of CASP1 in HCC cells may inhibit cell proliferation, but enhance cell survival and invasion abilities.