Infectious diseases are resulted from the invasion of an organism's body tissues by multiple disease-causing agents. It has been demonstrated that the occurrence and development of infectious diseases are closely associated with the functional status of immune system. Cytokines play significant roles in modulating the host immune response to the clearance of pathogenic microorganisms and maintaining immune homeostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specific pattern. With the progress of research in recent years, IL-35 might serve as an essential contributor in the immunopathogensis of vast infectious diseases, including hepatitis B, sepsis, tuberculosis and parasite infection, which simultaneously appear to be closely related to the severity, progression as well as prognosis of the illness. Apparently, IL-35 is regarded as a potent and promising anti-inflammatory cytokine in clinical application; its potential value may shed light on the therapeutic strategies for infectious diseases. Herein, we mainly review the potential role and its mechanism of IL-35 in the pathogenesis of infectious diseases.