CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. Here, we report that OTUD6A functions as a deubiquitinase of CDC6. OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6 protein expression.