Abstract: Due to the limited efficacy of chemotherapy, the prognosis of patients with advanced gastric cancer remains poor. There is still a need to optimize the treatments to improve the survival of these patients. Immune checkpoint inhibitors (ICIs) have changed the treatment strategies of advanced gastric cancer. Programmed death-1 (PD-1) inhibitor combined with chemotherapy with or without trastuzumab have brought new treatment options for HER2-negative and HER2-positive advanced gastric cancer patients, respectively. There are a series of ongoing studies to evaluate the efficacy of new ICIs, cancer vaccines, and adoptive cell immunotherapies. Moreover, screening the best beneficiaries of immunotherapy through biomarkers has become one of the hot research areas in gastric cancer. Besides tumor mutation burden (TMB), programmed death-ligand 1 (PD-L1) and microsatellite instability, emerging data suggested that circulating tumor DNA, gut microbiome and cytokines might also be the predictive biomarkers relevant to the effect of immunotherapy. In this review, we will summarize the results of the pivotal first-line immunotherapy clinical trials and biomarker exploratory studies in advanced gastric cancer.