〔Abstract〕 Objective Using RNA sequencing data from The Cancer Genome Atlas(TCGA) to explore the expression, mechanism, and clinical significance ofKCTD7in hepatocellular carcinoma(HCC). Methods The RNA sequencing data and clinical information of HCC patients were downloaded from the TCGA database. Univariate and multivariate Cox regression analyses were used to explore the correlation between the expression level of theKCTD7gene in HCC and the clinical information and prognosis of patients. Gene Set Enrichment Analysis(GSEA) was used to predict possible pathways regulated by theKCTD7gene in HCC. Single-sample GSEA(ssGSEA) was used to compare immune infiltration betweenKCTD7high expression group and low expression group.KCTD7knockdown HCC cell lines were established to explore its function and possible mechanism in HCC regulation. Results KCTD7was highly expressed in HCC tissues compared to normal tissues(P<0.01). The overall survival rate of HCC patients with high expression ofKCTD7gene was worse(P<0.05). The expression level ofKCTD7was an independent risk factor affecting the overall survival of HCC patients. GSEA results showed that theKCTD7gene was related to cell cycle signaling pathways. In the tumor microenvironment, high expression of theKCTD7gene was positively correlated with activated CD4+T cells, central memory CD4+T cells, and natural killer cells. Knocking downKCTD7might inhibit HCC cell proliferation, impair cell cycle distribution, and promote apoptosis. Conclusion KCTD7gene is highly expressed in HCC and affects the prognostic survival of HCC patients. Knocking downKCTD7can inhibit the proliferation of HCC cells and promote apoptosis.