In vivo experiments revealed that NSUN2 downregulation reduced GC tumorigenesis by decreasing EPYC level in vivo.<h4>Conclusion</h4>NSUN2-mediated m5C modification of EPYC contributed to GC cell growth and metastasis, which provided a novel regulatory axis for understanding the pathogenesis of GC. This evidence concerns the gene NSUN2 and gastric cancer.