Multicellular cytokine networks orchestrate the onset and progression of intestinal inflammation and colitis-associated cancer (CAC). Interleukin 22 (IL-22), a member of the IL-10 superfamily, is known for its ability to promote epithelial cell recovery and repair. However, dysregulation of IL-22 can inadvertently fuel intestinal inflammation and tumorigenesis through mechanisms that are not completely understood. Here we show that IL-22, derived from group 3 innate lymphoid cells (ILC3), directly triggers oncostatin M (OSM) responsiveness in intestinal epithelial cells by activating the transcription factor STAT3 and upregulating OSM receptor (OSMR) expression. OSM, a member of the IL-6 cytokine family implicated in inflammatory bowel disease, collaborates with IL-22 to sustain STAT3 activation in epithelial cells, thereby orchestrating proinflammatory epithelial adaptations and immune cell chemotaxis to the intestine. Conditional deletion of OSMR in epithelial cells protects mice from both colitis and CAC. Furthermore, pharmacological blockade of OSM reduces the progression of established CAC. Our study reveals a novel mechanism by which OSM sustains intestinal inflammation and CAC and identifies the IL-22-OSM axis as a promising therapeutic target for intestinal inflammation and tumorigenesis.