Interleukin (IL)-22 is gaining increased recognition for its role in modulating non-hematopoietic, stromal, and epithelial cells during chronic inflammatory diseases. IL-22 is produced by CD4 T-cell subsets of the adaptive immune system and by innate lymphocytes, including natural killer (NK) cells, innate lymphoid cells (ILCs) and lymphoid tissue inducer (LTi)-like cells. IL-22 utilizes a heterodimeric receptor (R) consisting of IL-22Rα and IL-10Rb, which are expressed by epithelial cells, to activate the Stat3 signalling cascade and the Akt and mitogen-activated protein kinase pathways. We examined the role of IL-22 during tumour promoting inflammation, a recent addition to the ‘hallmarks of cancer’. Our results demonstrate that IL-22 gene expression is elevated in both human and mouse intestinal-type gastric cancer (IGC). IGC is associated with chronic inflammation and excessive Stat3 activation, which are crucial to gastric tumour progression in mice1. Here we provide the first evidence that therapeutic inhibition of IL-22 signalling leads to a reduction in gastric tumour burden in mice. Inhibition of IL-22 signalling was linked to attenuated gastric epithelial Stat3 activation and dampened downstream pro-survival pathways. We identified the cellular source of IL-22 within the gastric tumours, and confirmed that immune cells in the microenvironment are a prominent source of tumour promoting cytokines. Taken together, our results highlight cytokine inhibition as an emerging therapeutic opportunity for inflammation-associated cancers.