The present review indicates that the IL-22-IL-22R axis plays significant physiological and pathological functions in the progression of NAFLD, and pharmacological treatment with exogenous IL-22 or IL-22-producing agents can relieve disease severity via multiple mechanisms, suggesting that IL-22 can be utilized as a novel target for NAFLD intervention. This evidence concerns the gene IL22RA1 and metabolic dysfunction-associated steatotic liver disease.