Background Prognostic biomarkers remain a focus in breast cancer during last decades. More reliable predictors to adequately characterize the prognosis of breast cancer are essential. The 2 '-5 '-oligoadenylate synthetases (OAS), composing of OAS1, OAS2, OAS3, and OAS-like (OASL), are interferon (IFN)-induced antiviral enzymes, with their prognostic roles remain to be characterized. Methods Prognostic values of OAS family members were assessed by multiple public available resources. Results High mRNA expression of OAS1 and OAS3 were correlated with worse prognosis for all breast cancer patients, whereas OAS2 was associated with favorable prognosis. The prognostic values of OAS family in different clinicopathologic subtypes were also characterized. In DNA methylation level, cg12560128 in OAS2, cg06800840 and cg26328872 in OASL showed significant prognostic values. The mRNA expression of OAS members signature in high/low risk overall survival groups was opposite to the high/low risk recurrence free survival groups. Neutrophil cell exhibited highest correlation with all OAS members in tumor immune infiltrating estimation. Conclusions This study provided new insight into the prognostic roles of OAS in breast cancer with potential mechanistic values.