Abstract: In the field of tumor therapy research, Agaricus blazei Murrill(ABM), a valuable edible mushroom with both nutritional and medicinal properties, has attracted significant attention for its antitumor potential. To date, a comprehensive systematic review of its antitumor mechanisms remains lacking. Studies indicate that active compounds in ABM exert antitumor effects through multi-target and multi-pathway synergistic mechanisms, including inducing tumor cell apoptosis, arresting the cell cycle, suppressing tumor angiogenesis, and modulating the tumor immune microenvironment. Clinically, ABM extracts synergize with chemotherapeutic agents to reverse tumor cell multidrug resistance, alleviate adverse effects of radiotherapy and chemotherapy, and enhance immune function and quality of life in patients. However, challenges persist, such as unclear mechanisms of action of active components, limited clinical data, and low bioavailability. Future research could integrate nanocarrier technology to optimize drug delivery strategies and conduct high-quality clinical trials to validate its safety and efficacy. This review aimed to systematically synthesize current knowledge on the antitumor mechanisms of ABM-derived bioactive compounds, including polysaccharides, sterols, terpenoids, and polyphenols, and critically analyze clinical research progress. By providing a robust theoretical foundation and actionable insights, this work seeks to advance the translational potential of ABM in oncology.