Kinesin family member 20A (KIF20A) is an essential regulator of cytokinesis. In this study, by performing a retrospective study based on data from the Cancer Genome Atlas (TCGA)-Liver and Hepatocellular Carcinoma (LIHC) cohort, we tried to assess the independent prognostic value of KIF20A in terms of overall survival (OS) and recurrence-free survival (RFS). Results showed that normal liver tissues had very low KIF20A expression compared with normal tissues in other cohorts in TCGA. However, the primary HCC tissues (N = 371) had significantly elevated KIF20A expression than normal liver tissues (N = 50). Immunohistochemistry (IHC) data showed that normal hepatocytes had weak KIF20A staining. In comparison, some HCC tissues had medium and strong KIF20A expression, with nuclear-enhanced staining. By grouping patients with primary HCC (N = 365) into high and low KIF20A expression groups, we found that the high expression group had a substantially higher proportion of high-grade tumors (G3/G4) (34/65, 52.3% vs. 96/295, 32.5%, P = 0.0027), advanced tumors (stage III/IV) (28/61, 45.9% vs. 59/280, 21.1%, P < 0.0001) and death (44/67, 65.7% vs. 86/298, 28.9%, P < 0.0001) compared with the low expression group. Kaplan-Meier curves of OS and RFS indicated that high KIF20A expression was associated with worse survival outcomes. Subgroup analysis confirmed the associations in G1/G2, G3/G4 tumors and in early and advanced stages. Following univariate and multivariate analysis revealed that KIF20A expression was an independent prognostic indicator for poor OS (HR: 1.304, 95%CI: 1.157-1.469, P < 0.001) and RFS (HR: 1.144, 95%CI: 1.028-1.272, P < 0.001). Based on these findings, we infer that KIF20A was aberrantly expressed in HCC tissues and its expression might independently predict poor OS and RFS. © 2018 IUBMB Life, 70(4):328-335, 2018.