BACKGROUND: Hip2, a ubiquitin-conjugating enzyme, has been shown to modulate the stability of cyclin B1, a cell cycle regulator. However, the function of Hip2 in gastric cancer (GC) remains largely elusive. METHODS: The expression of Hip2 in GC cell lines was analyzed by RT-qPCR, Western Blotting and Immunohistochemical Staining. shRNA was utilized to knock down the expression of Hip2. Cell growth, cell cycle, migration, invasion and tumorigenesis were performed by CCK-8, BrdU staining, flow cytometry, wound healing, transwell migration and invasion, and xenograft assay, respectively. RESULTS: Hip2 was highly expressed in GC cell lines and patients. High level of Hip2 indicated poor prognosis. Knockdown of Hip2 suppressed cell growth, lead to G2/M phase arrest, and reduced cell migration and invasion in vitro. Furthermore, downregulation of Hip2 inhibited tumorigenesis in vivo. CONCLUSIONS: Elevated expression of HIP2 in GC patients suggested poor prognosis. Reduction of Hip2 suppressed GC progression, indicating that Hip2 may be a potential target for the management of GC.