Background: Stomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in the cancer-related deaths among all malignances. The prognosis of STAD is poor. Immunotherapy based on immune checkpoint blockade is ever-increasingly suggested as the most promising therapy strategy for STAD. However, the prognosis and therapy value of immune checkpoints in STAD is far from clarified. Methods: In our study, bioinformatics methods were performed to explore the expression and prognosis value of immune checkpoints in STAD and their association with immune infiltration. qRT-PCR was performed to verify our result. Results: Most of the immune checkpoints were upregulated in STAD. There were lots of genetic mutations among immune checkpoints in STAD, including missense_mutation, frame_-shift_del et al. Interestingly, most of immune checkpoints were associated with drug sensitivity and drug resistance. Moreover, CD274, PVR, LGALS9, ICOSLG and CD70 were associated with the overall survival, post progression survival and first progression in STAD. The univariate and multivariate analysis revealed that CD70, ICOSLG, age, pTNM stage, and radiation therapy were independent factors affecting the prognosis of STAD patients. The expression of ICOSLG and CD70 was correlated with immune cells as well as immune biomarkers, including CD8+ T cells, CD4+ T cells, macrophage, neutrophils and dendritic cells. Conclusion: All in all, our study performed a comprehensive analysis of the prognostic value and immune function of immune checkpoints in STAD, and our result suggested that immune checkpoint ICOSLG and CD70 serve as prognostic biomarkers and associate with immune infiltration in STAD.