Bufalin is an active compound of the traditional Chinese medicine Chansu, which exhibits significant anti-tumor activities in many solid tumors and leukemia cell lines. Bufalin could introduce apoptosis, reverse drug-resistance, and prevent migration and invasion of tumor cells. This paper reviewed the latest research progress of the in vitro and in vivo anti-tumor effect and mechanism of bufalin on a series of cancers, such as hepatocellular carcinoma, lung cancer, colon cancer, gastric cancer, leukemia, bladder cancer, and its formulation study is also summarized for the reference of its further study and application.