Cancer is a leading cause of death worldwide. Recently, the demand for more effective and safer therapeutic agents for the chemoprevention of human cancer has increased. As a white rot fungus, Inonotus obliquus is valued as an edible and medicinal resource. Chemical investigations have shown that I. obliquus produces a diverse range of secondary metabolites, including phenolic compounds, melanins, and lanostane-type triterpenoids. Among these are active components for antioxidant, antitumoral, and antiviral activities and for improving human immunity against infection of pathogenic microbes. Importantly, their anticancer activities have become a hot recently, but with relatively little knowledge of their modes of action. Some compounds extracted from I. obliquus arrest cancer cells in the G0/G1 phase and then induce cell apoptosis or differentiation, whereas some examples directly participate in the cell apoptosis pathway. In other cases, polysaccharides from I. obliquus can indirectly be involved in anticancer processes mainly via stimulating the immune system. Furthermore, the antioxidative ability of I. obliquus extracts can prevent generation of cancer cells. In this review, we highlight recent findings regarding mechanisms underlying the anticancer influence of I. obliquus, to provide a comprehensive landscape view of the actions of this mushroom in preventing cancer.