BACKGROUND: Reflux esophagitis is a common gastrointestinal disorder characterized by significant inflammatory responses. The NLRP3 inflammasome plays a crucial role in inflammation, and miR- 223 - 3p has been found to inhibit its expression by targeting NLRP3 mRNA. This study aims to further investigate the mechanism by which miR- 223 - 3p inhibits reflux esophagitis through targeting the NLRP3 inflammasome. METHODS: A reflux esophagitis cell model was constructed to assess the expression levels of miR- 223 - 3p and NLRP3. Overexpression and inhibition techniques were used to study the effects of miR- 223 - 3p on the NLRP3 inflammasome. qPCR and Western blot analyses were employed to detect the expression of related inflammatory factors, and flow cytometry was used to assess cell apoptosis and cell cycle changes. RESULTS: The study found that miR- 223 - 3p was significantly downregulated in the reflux esophagitis model, while NLRP3 and its downstream inflammatory factors were significantly upregulated. Overexpression of miR- 223 - 3p markedly inhibited NLRP3 expression, reduced the release of inflammatory factors, decreased cell apoptosis, promoted cell cycle progression, and enhanced cell viability. Overexpression of NLRP3 reversed these protective effects of miR- 223 - 3p, further confirming that miR- 223 - 3p alleviates inflammation by inhibiting the activation of the NLRP3 inflammasome. CONCLUSION: This study demonstrates that miR- 223 - 3p plays a key role in reducing inflammation and cellular damage in reflux esophagitis by targeting the NLRP3 inflammasome. These findings provide new insights and potential therapeutic targets for the treatment of reflux esophagitis.