Aim: To explore the prognostic value of the cell division cycle-associated proteins (CDCA) family in clear cell renal cell carcinoma. Methods: Gene profiles were collected from the The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), the GSE29609 and GSE22541 datasets. Genetic alteration and DNA methylation data were downloaded from the cBioPortal and MethSurv. The functional enrichment data were analyzed by Metascape. Results: The mRNA expression of the CDCAs, except CBX2, was significantly increased in clear cell renal cell carcinoma patients. Genetic alterations might affect the expression of CDCAs, but promotor methylation does not affect CDCA gene expression. The overall expression of the CDCAs, according to the The Cancer Genome Atlas-KIRC database (hazard ratio [HR]: 2.18), the GSE29609 (HR: 6.08) and GSE22541 (HR: 6.73), was significantly associated with unfavorable overall survival. In addition, genes co-expressed with CDCAs (R2 ≥0.3) were highly associated with cell division and the FOXM1 pathway. Conclusion: Our study demonstrated that the aberrant expression of CDCA gene family members plays an indispensable role in tumorigenesis.