Interleukin (IL)-27, a member of the IL-6/IL-12 family, has an important role in modulating inflammation in partnership with innate and adaptive immune cells. IL-27 binding to IL-27R starts downstream signaling based on the target cells. It can instigate inflammation by inducing CD4 T cell proliferation, Th1 polarization, cytotoxic T cell activation, generation of the natural killer cell, and macrophage and dendritic cell activation. However, by inducing programmed cell death and suppression of effector cells, IL-27 can suppress inflammation and return the immune response to hemostasis. Altogether, IL-27 displays multifaceted dual functions, which may result in either pro- or anti-inflammatory effects. Recent investigations indicated the antitumor activity of IL-27 via inducing Th1, and CTL responses and generating NK cells. On the other hand, IL-27 also can promote tumor cells' proliferation, survival, and angiogenesis. In the present review, we'll discuss recent advances concerning the role of IL-27 in inflammatory diseases such as infections, autoimmune diseases with a focus on cancer.