Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.