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Gastrointestinal malignant tumors are a group of severely life-threatening tumors. Their incidence and mortality rates consistently rank among the top 10 cancers worldwide and are increasing year by year. Based on his long-term clinical practice, Professor Zhou Zhongying proposes the theory of "cancer toxin". The research team led by Professor CHENG Hai-bo further establishes the pathogenesis theory of cancer toxin, holding that cancer toxin is the key factor in the occurrence and development of tumors, and thus taking "anti-cancer and detoxification" as the basic therapeutic principle. With the vigorous promotion of TCM, various active ingredients of TCM are extracted and make a difference in tumor therapy. These active ingredients can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an active ingredient extracted from the skin of Bufo gargarizans with detoxifying, anti-swelling, and pain-relieving effects and is widely used in the treatment of intermediate and advanced tumors. Clinical studies have revealed that cinobufotalin enhances tumor control rates, prolongs survival time, improves quality of life, and reduces the incidence of adverse reactions when combined with chemotherapy, radiotherapy, or targeted therapies. The mechanism studies have demonstrated that cinobufotalin plays a therapeutic role by inhibiting cell proliferation and invasion, inducing tumor cell apoptosis, modulating immune response, reversing drug resistance, etc. This paper reviews the research progress on cinobufotalin from the perspective of pathogenesis theory of cancer toxin through summarizing domestic and international reported research on clinical application and mechanism of cinobufotalin against gastrointestinal malignant tumors in recent years. The findings aim to provide a theoretical basis for research on the anti-tumor effect of cinobufotalin and a reference for standardized use and in-depth research of drugs.