Ubiquitin-specific protease 14 (USP14) is one of the three proteasome-associated deubiquitinating enzymes and implicated in the progression of various cancers. However, the role of USP14 in ovarian cancer remains unknown. By using an unbiased qRT-PCR screen, here we show that USP14 is considerably increased in cisplatin-resistant ovarian cancer cells. Overexpression of USP14 confers resistance to cisplatin-sensitive ovarian cancer cells. Genetic or pharmacological inhibition of USP14 is able to reverse cisplatin-resistance of ovarian cancer cells, which was accompanied by decreased protein expression of BCL6. Besides, BCL6 protein level was also increased in cisplatin-resistant ovarian cancer cells and silencing of BCL6 in these cells restored their sensitivity to cisplatin. At the molecular lever, we found that USP14 interacted with BCL6 and prevented it from proteasomal-dependent degradation. Thus, our results provide a rationale to target USP14-BCL6 axis in ovarian cancer that may be therapeutically beneficial. (C) 2020 Elsevier Inc. All rights reserved.