SUZ12 is a core component of the polycomb repressive complex 2 (PRC2), which could silence gene transcription by generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3). Meanwhile, SUZ12 has been found to be overexpressed in multiple cancers; however, the clinical significance and molecular mechanisms of SUZ12 controlling gastric cancer cell proliferation and metastasis are unclear. In this study, we found that SUZ12 expression was significantly increased in 64 gastric tumor tissues compared with normal tissues. Additionally, SUZ12 expression was associated with pathological stage, metastasis distance, and shorter overall survival of gastric cancer patients. Knockdown of SUZ12 expression impaired cell proliferation and invasion in vitro, leading to the inhibition of metastasis in vivo. Upregulation of SUZ12 was found to play a key role in gastric cancer cell proliferation and metastasis through the regulation of EMT and KLF2 expression.