--- - |2 Summary Cancer immunotherapy has been increasingly applied in the treatment of advanced malignancies. Consequently, immune checkpoints have become a major concern. As PD‐1 is an important immunomodulatory protein, the blockade of PD‐1 and its ligand PD‐L1 is a promising tumour immunotherapy for human carcinoma. In this review, we first discuss the role of the PD‐1/PD‐L1 interaction in gastrointestinal tract cancers. Targeting PD‐1 and PD‐L1 in immune cells and tumour cells may show remarkable efficiency in gastrointestinal tract cancers. Second, the PD‐1/PD‐L1‐associated signalling pathway involved in cancer immunotherapy in gastrointestinal tract cancers is discussed. Most importantly, this review summarizes the PD‐1/PD‐L1‐targeted immunotherapy combinations with relevant signalling pathways, which may result in a breakthrough for the treatment of gastrointestinal tract cancers, such as gastric cancer, colorectal cancer and liver cancer. Meanwhile, the review provides a deeper insight into the mechanism of checkpoint blockade immunotherapies. - 'Clinical and Experimental Pharmacology and Physiology, EarlyView. '