In the current study, we investigated the interactions between tumour cells, CAFs, and tumour-associated neutrophils (TANs) in the gastric cancer microenvironment, identified lysine[K]-specific demethylase 5B (KDM5B) as the transcription factor of IL-8 in CAFs, and demonstrated that tumour cell-derived serglycin (SRGN) mediated by TANs promotes IL-8 production via upregulating KDM5B expression in CAFs. Here, SRGN is linked to gastric cancer.