SNHG5 exerted its function through interacting with MTA2, preventing the translocation of MTA2 from the cytoplasm into the nucleus. SNHG5 overexpression led to significant increases in the acetylation levels of histone H3 and p53, indicating that SNHG5 might affect acetylation by trapping MTA2 in the cytosol, thereby interfering with the formation of the nucleosome remodeling and histone deacetylation complex. This study is the first to demonstrate that SNHG5 is a critical and powerful regulator that is involved in GC progression through trapping MTA2 in the cytosol.