Interferon Epsilon (IFNe) is a distinct member of the type I IFN family with unique properties due to its constitutive expression by epithelium of the female reproductive tract, regulation by hormones and not apparently via pattern recognition receptor mediated pathways that respond to infections, DNA damage and other insults. It regulates mucosal immune responses to infections by its intrinsic antiviral and antibacterial properties and by activating immune effectors including NK and CD8 T cells1. We show here that both endogenous and exogenous IFNe inhibits growth of ovarian tumours in the peritoneum. We use syngeneic and PDX models to determine the mechanism of action of the anti-tumour effects of IFNe. It signals via canonical type I IFN receptors IFNAR1 and IFNAR2, activates some conventional JAK/STAT pathways, Consequently, IFNe has direct effects on tumours that can inhibit proliferation, stimulate apoptosis pathways and modulate cell surface levels of immune interaction proteins MHC, checkpoint molecules and tumour antigens. We demonstrate that IFNe is also a potent regulator of many arms of the anti-tumour immune response including CD* and NK cells which are particularly effective in inhibiting peritoneal metastases in models of ovarian cancer.