As the core factor of tumor immune escape, CD47 sends a ‘don't eat me’ signal to macrophages by binding with receptor signal regulatory protein (SIRP)α, enabling tumor cells to evade immune clearance and promoting the progression of tumors. CD47-SIRPα axis not only regulates the homeostasis of red blood cells, Plt, hematopoietic stem cells and neurons, but also plays an adaptive immunomodulatory role resembling PD-1/PD-L1 in tumors. Multiple regulatory factors, including cytokines, oncogenes, microRNA(miR) and enzymes, are involved in the regulation of CD47 expression in tumor cells, among which IL-1, miR-340 and miR-128 have been confirmed to specifically regulate the expression level of CD47 in pancreatic cancer. Recent clinical trials show that anti-CD47 antibody has significant therapeutic potential for pancreatic cancer with low response rate to PD-1, and the adverse reactions are mainly grade 1-2 hematotoxicity, which is well controllable. Existing strategies adopted to control toxicities include dose adjustment, construction of bispecific antibodies that reduce the binding capacity of red blood cells, blocking other sites of CD47-SIRPα axis and developing novel targeted delivery systems. Anti-CD47 therapy combined with other immunotherapies shows its therapeutic potential in HER2-positive gastric cancer, which provides a new perspective for neoadjuvant therapy and comprehensive therapy for pancreatic cancer and is expected to significantly improve clinical prognosis of patients.