Endoplasmic reticulum (ER) stress has a significant impact on cell growth, proliferation, metastasis, invasion, chemotherapy resistance, and angiogenesis in various cancers. However, the effect of ER stress on the outcome of osteosarcoma patients is still unclear. In this study, we established an ER stress risk model based on the Cancer Genome Atlas for osteosarcoma dataset to reflect immune features and predict the prognosis of osteosarcoma patients. Survival analysis showed significant differences in overall survival among osteosarcoma patients with different ER stress-related risk scores. Additionally, ER stress-related risk features were significantly associated with clinical and pathological characteristics of osteosarcoma patients and served as independent prognostic indicators. Functional enrichment analysis revealed that the risk model was associated with cell chemotaxis, leukocyte migration, and regulation of leukocyte migration. Moreover, the ER stress-related risk model indicated the presence of an immunosuppressive microenvironment and immune checkpoint responses in osteosarcoma. In conclusion, we proposed an ER stress risk model that is an independent prognostic factor and indicates general immune features in the microenvironment of osteosarcoma.