Abstract: AT-rich interactive domain 1A (ARID1A) is a subunit of SWItch/Sucrose non-fermentable complexes and one of the most frequently mutated chromatin regulators in all types of tumors. Most of these mutations are frameshift or nonsense mutations. ARID1A is a tumor suppressor gene, and its mutation or loss of expression may lead to development and progression of neoplasia via different molecular pathways. ARID1A mutations or loss of expression is associated with high programmed cell death-ligand 1 (PD-L1) expression, Epstein-Barr virus (EBV) positivity, microsatellite instability-high (MST-H) status, high tumor mutation burden (TMB), and abundant tumor-infiltrating lymphocytes (TILs) in gastric cancer. Studies have found that immune checkpoint inhibitors can significantly prolong the progression-free survival of cancer patients with ARID1A deficiency. In this article, we review the possible pathways mediating ARID1A mutations or loss of expression leading to tumorigenesis and the relationship between ARID1A deficiency and immunotherapy response in gastric cancer.