Gasdermin B (GSDMB) belongs to the gasdermin (GSDM) family which may adopt different mechanisms of intramolecular domain interactions to modulate their lipid-binding and pore-forming activities. The GSDM family has regulatory functions in cell proliferation and differentiation, especially in pyroptosis process. Pyroptosis is a pro-inflammatory form of regulated cell death and is designed to attract a nonspecific innate response to the site of infection. For cancer cells, the activation of pyroptosis may promote cell death and exert anticancer properties. Also, recent studies have observed the pyroptosis-like features in GSDMB and some researches have shown that GSDMB overexpression occurred in several kinds of cancers; these findings bring a contradiction with the participation of GSDMB in pyroptosis. Although people pay less attention to GSDMB, it still has some essential research value. It is a paradox that GSDMB might participate in programmed cell death, which might put forward a research direction of therapeutic targets for cancer. Here, we review the possible progress of how GSDMB participated in this inflammatory regulation mechanistically and the potential functions of GSDMB in cancer.