The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo. Moreover, luciferase reporter assay, western blot analysis and microribonucleoprotein immunoprecipitation were performed to determine that miR-665 directly repressed XBP1 (X-box-binding protein-1) and ORMDL3 expression. This evidence concerns the gene XBP1 and colitis.