Using an in vitro model, we demonstrate that CAFs-derived IL-33 promotes migration, invasion and epithelial–mesenchymal transition (EMT) of GC cells by activation of the ERK1/2/SP1/ZEB2 pathway via ST2L, and that in turn, GC cell derived-TNF-α upregulates IL-33 expression in CAFs via the TNFR2/NF-κB/IRF-1 pathway. The gene discussed is ZEB2; the disease is gastric cancer.