background: Preeclampsia can cause severe consequences for pregnant women and infants, and developing effective medicine or methods to prevent or treat patients with preeclampsia is urgently needed. Ubiquitin-specific protease 14 (USP14) has emerged as a critical regulator in the development of human cancers and neurodegenerative diseases. However, its role in preeclampsia remains elusive. methods: The expression of USP14 in placental tissues from healthy donors and preeclampsia patients were determined by quantitative reverse transcription PCR assay. The protein levels of targeted genes were evaluated by Western blotting assay. Small interfering RNA-mediated gene knockdown was used to reduce USP14 expression in trophoblast cell lines. results: The expression levels of USP14 and proinflammatory cytokine were substantially upregulated in placental tissues from preeclampsia patients. Knockdown or inhibition of USP14 significantly abrogated hypoxia/reoxygenation-induced upregulation of nuclear factor kappa B (NF-κB) activation and proinflammatory cytokine production. conclusions: Our results suggested that USP14 promotes proinflammatory cytokine production through activation of NF-κB. Developing drugs targeting USP14 may be beneficial for the prevention or treatment of patients with preeclampsia.