Intestinal metaplasia (IM) refers to the replacement of gastric epithelial cells by intestinal epithelial cells. This is often accompanied by chronic atrophic gastritis (CAG), which is a precancerous lesion of gastric cancer. The incidence rates of CAG and IM are increasing gradually, which generates an enormous economic burden to individuals and society. To explore the pathogenesis of CAG with IM, we screened out the differentially expressed gene olfactomedin 4 (OLFM4) by bioinformatics and constructed OLFM4-shRNA plasmid chitosan magnetic nanoparticles to knockdown this gene. This caused a downregulation of caudal type homeobox 2 (CDX2), a marker of IM, suggesting that knocking down OLFM4 may slow the pathological process of IM, thus providing putative relevant targets for the treatment of CAG with IM.