Objectives: Oral epithelial cells (OECs) represent the first line of defense against viruses spread via saliva. One method cells use to suppress viral infections is the production of interferons (IFNs). However, not much is known about the IFN expression profiles of OECs. The goal of this study is to define the differential expression of IFNs in OECs. Methods: Immortalized human oral keratinocytes (OKF6/Tert-1) were subjected to RNA sequencing analysis to determine the baseline level of IFN expression. OKF6/Tert-1 cells were also treated with one of two pathogen associated molecular patterns (PAMPs) that mimic viral infections: 1 μg/ml polyinosinic:polycytidylic acid (poly(I:C)) or 5 μM unmethylated CpG DNA. RT-qPCR was performed on the RNA extracted from the cells to measure different IFN subtypes: alpha, beta, gamma, epsilon, kappa, and lambda. Results: IFNK and IFNE transcripts were highly expressed in OKF6/Tert-1 cells at baseline conditions. Treatment of one or more PAMPs led to the upregulation of other IFN subtypes, including IFNA (multiple subtypes), IFNB1, IFNG, IFNE, and IFNL (multiple subtypes). Conclusions: OECs differentially express multiple types of IFN. IFN-kappa and IFN-epsilon seem to be constitutively expressed and may act as a constant source of priming OECs against virus. Other IFNs are upregulated when in the presence of PAMPs that mimic viral infections, suggesting their role as responders to viral infection. Several of these IFN subtypes, including IFN-kappa and IFN-epsilon have not been previously shown to be expressed in OECs and represent novel targets of therapies to help defend against viral infections spread via saliva.