Abstract: In cancer development and progression, tumor cells escape from the surveillance of our immune system. Understanding the mechanism behind this phenomenon is crucial in developing new anti-cancer therapies. Immunotherapy, which aims to trigger the immune reaction of the patient's own immune system, stands in the spotlight of cancer research and has promising applications. CD47 is ubiquitously expressed in many kinds of cells serving as a "do-not-eat-me" signal. Cancer cells may take advantage of CD47 overexpression to escape from immunosurveillance. Cancer stem cells have high expression levels of CD47. Blocking the interaction between CD47 and SIRPα can induce targeted phagocytosis of cancer cells. Several clinical trials on three different kinds of CD47-targeted drugs are ongoing, but the animal models used may have a potential issue in estimating clinical efficacy. The present study aims to review the development and current status of anti-CD47 anti-cancer therapy, raise the concerns on the animal models, and discuss some perspectives on future clinical applications.