IL-27 is structurally an immune-enhancing and pleiotropic two-chain cytokine associated with IL-12 and IL-6 families. IL-27 contains two subunits, namely IL-27p28 and EBI3. A heterodimer receptor of IL-27, composed of IL27Rα (WSX1) and IL6ST (gp130) chains, mediates the IL-27 function following the activation of STAT1 and STAT3 signaling pathways. Specifically, IL-27 is identified as augmenting cytokine of immune responses, including Th1 cell differentiation, TCd4 + cell proliferation, and IFN-γ production with the help of IL-12. According to several published studies, due to the pro-inflammatory or anti-inflammatory functions of cytokine related to the biological context in various disorders and diseases, IL-27 has been considered a complex regulator of the immune system. Surprisingly, the dual role of IL-27, the same as the double-edged sword, has also been evidenced in clinical models of various hematological or solid tumors. Predominantly, Il-27 applies anti-tumor functions by inducing the responses of a cytotoxic T lymphocyte (CTL) and Th1 and suppressing the growth, proliferation, angiogenesis, invasiveness, metastasis, and survival of tumor cells. On the other hand, IL-27 may also play a protumor role in cancers and induce tumor progression. The current update study aimed to summarize the protumor anti-tumor and biological functions of IL-27 in different hematological malignancies and solid tumors.