The tumor immune microenvironment can provide prognostic and predictive information. A previously validated ImmunoScore of gastric cancer (ISGC) evaluates both lymphoid and myeloid cells in the tumor core and invasive margin with immunohistochemistry staining of surgical specimens. We aimed to develop a noninvasive radiomics-based predictor of ISGC.In this retrospective study including four independent cohorts of 1778 patients, we extracted 584 quantitative features from the intratumoral and peritumoral regions on contrast-enhanced CT images. A radiomic signature (RIS) was constructed to predict ISGC by using regularized logistic regression. We further evaluated its association with prognosis and chemotherapy response.A 13-feature radiomic signature for ISGC was developed and validated in 3 independent cohorts (area under the curve=0.786, 0.745, and 0.766). The RIS signature was significantly associated with both disease-free and overall survival in the training and all validation cohorts (HR range: 0.296-0.487, all P<0.001). In multivariable analysis, the RIS remained an independent prognostic factor adjusting for clinicopathologic variables (adjusted HR range: 0.339-0.605, all P<0.003). For stage II and III disease, patients with a high RIS derived survival benefit from adjuvant chemotherapy, HR=0.436 (95% CI: 0.253-0.753), P=0.002; HR=0.591 (95% CI: 0.428-0.818), P<0.001, respectively; while those with a low RIS did not.The radiomic signature is a reliable tool for evaluation of immunoscore and retains the prognostic significance in gastric cancer. Future prospective studies are required to confirm its potential to predict treatment response and select patients who will benefit from chemotherapy.