Strategies in comprehensive therapy for gastrointestinal (GI) cancer have been optimized in the last decades to improve patients’ outcomes.However,treatment options remain limited for late-stage or refractory diseases.The efficacy of immune checkpoint inhibitors (ICIs) for treatment of refractory GI cancer has been confirmed by randomized clinical trials.In 2017,pembrolizumab was approved by the US Food and Drug Administration as the first agent for treatment of metastatic solid tumors with mismatch repair deficiency,especially for colorectai cancer.Given the different mechanisms,oncologists have focused on determining whether ICIs-based combination strategies could achieve higher efficacy than conventional therapy alone in late-stage or even front-line treatment of GI cancer.This review discusses the current status of combining immune checkpoint inhibitors with molecular targeted therapy,chemotherapy,or radiotherapy in GI cancer in terms of mechanisms,safety,and efficacy to provide basis for future research.