Background: The members of the cell division cycle-associated ( CDCA ) gene family are significant regulators of cell proliferation known to play key roles in various cancers. However, the function of CDCA genes in hepatocellular carcinoma (HCC) is unclear. The aim of this research was to clarify the roles of CDCA family members in HCC using bioinformatics analysis tools., Methods: We studied data on the mRNA and protein expression of CDCA genes and survival in patients with HCC using the Oncomine, UALCAN, HPA, CCLE, LinkedOmics, cBioPortal, and Metascape databases., Results: Significant overexpression of all CDCA members was found in HCC tissues. The expression levels of CDCA s were related to the tumor stage, and high expression levels were correlated with a low survival rate in patients with HCC. Also, we observed a high mutation rate (45%) of CDCA s in the HCC samples, which manifested as deep deletion, amplification, or increased mRNA expression. In the correlation analysis, we found that any 2 CDCA members were significantly positively correlated with each other. Cycle-related genes including AHCTF1 , AKT1 , BIRC5 , CENPF , CENPL , and CENPQ were closely associated with CDCA gene alterations., Conclusions: The findings of this study indicate that CDCA s may be potential therapeutic targets and prognostic indicators for patients with HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-21-110). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)