Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation. Significantly, co-immunoprecipitation (Co-IP) analyses indicated that ESCO2 can interact with p53 in GC cells. Taken together, our data demonstrate that ESCO2 is essential for the development of GC and might be a potential therapeutic target for treating GC. (C) 2018 Elsevier Inc. All rights reserved.