understanding of the disease is constantly updated, just as strategies for treating malignant tumors are constantly updated. New diagnoses, follow-up indicators, and treatment plan formulations need more evidence to be supported. To date, radical surgical resection is still the preferred treatment for advanced digestive system malignancies, and combination therapy including chemotherapy and targeted therapy before or after surgery is aimed at improving the prognosis and quality of life of patients. However, if tumor recurrence, metastasis, chemotherapy, and drug resistance to targeted agents after surgery prevent the achievement of the desired therapeut ic effect, and if neoadjuvant chemotherapy and targeted therapy cannot reduce the staging of the tumor, surgery cannot be performed. These are huge problems that we face now and will continue to face for some time.Relevant scientific data and evidence have been produced to explain unsatisfactory efficacy, such as epithelial-mesenchymal transformation, the tumor microenvironment, extracellular matrix p roteins, cancer-related fibroblasts, and other factors that may be related to tumor progression and poor therapeutic effects. An extracellular matrix protein, periostin (POSTN), influences the above factors and has received multidisciplinary attention. In this paper, periostin and digestive system-related tumors are reviewed, and the production, mechanism of action, drug resistance correlation analysis, and coping strategies of periostin are summarized to further understand its characteristics. This work provides evidence for potential therapeutic targets for digestive system tumors in the future.