Objectives: Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disease characterized by thrombocytopenia. This review will examine the Notch-aromatic hydrocarbon receptor (AhR)-interleukin-22 (IL-22) signaling pathway regulatory mechanisms in ITP to generate ideas for the pathogenesis and etiological investigation of the disease. Mechanism: Studies had shown that an abnormal imbalance of immune cells and immune factors is associated with ITP pathogenesis. The Notch-AhR-IL-22 signaling pathway disrupts the immune microenvironment in vivo, which contributes to the pathogenesis of ITP. Findings in Brief: Several studies have suggested that the pathogenesis of ITP may be mediated by multiple pathways, such as Notch signaling that induces AhR to increase direct secretion of IL-22 from CD4{}^{+}T cells or the Notch-AhR pathway that induces differentiation of CD4{}^{+}T cells into Th22 cells to enhance IL-22 expression. However, the precise pathogenic mechanisms are still unknown. Conclusions: ITP pathogenesis is complex, the Notch-AhR-IL-22 signaling pathway may be involved in the pathogenesis of ITP, and further research into the relationship between ITP and this signaling pathway is needed.