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Previous studies have demonstrated that the aberrant expression of deubiquitinating enzymes (DUBs) is closely associated with cancer progression, including gastric cancer (GC), due to its role in maintaining protein stability. The 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a member of the DUBs family, is reported to be highly expressed in some types of cancer and its overexpression indicates poor prognosis, but the function of PSMD14 in GC remains unclear. To investigate this issue, we first analyzed the PSMD14 expression via the TNMplot database and found that PSMD14 was up-regulated in GC tissues compared with the adjacent normal tissues (P < 0.01). PSMD14 knockdown notably inhibited cell proliferation, migration, and invasion in vitro , which was confirmed through in vivo experiments. However, PSMD14 overexpression presented the opposite effects. Additionally, we found that PSMD14 deletion inhibited the protein level of polypyrimidine tract-binding protein 1 (PTBP1), an activator of GC development. Further investigation confirmed that PSMD14 and PTBP1 presented co-localization and had an endogenous interaction. PSMD14 was revealed to promote the deubiquitination and stabilization of PTBP1, and PTBP1 knockdown reversed the effects caused by PSMD14 overexpression on cell function. Collectively, we demonstrate that PSMD14 as a deubiquitinating enzyme may promote the development of GC via stabilizing PTBP1, which provides a theoretical basis for a therapeutic target against GC. • PSMD14 was highly expressed in gastric cancer (GC) samples and cell lines. • PSMD14 notably promotes GC cell proliferation, migration, invasion and the growth of xenograft tumors in vivo. • PSMD14 promotes the deubiquitination and stabilization of polypyrimidine tract-binding protein 1 (PTBP1) in GC cells. • PTBP1 mediates the promoting effect of PSMD14 on the development of GC. [ABSTRACT FROM AUTHOR]