The human IFNL gene family consists of four members, IFNL1, IFNL2, IFNL3, and IFNL4. Genetic polymorphisms within the IFNL loci genes are associated with both spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. The IFNL4 gene is suggested to be the causal gene, however the expression levels of IFNL4 mRNA in hepatocytes is surprisingly low in humans. In order to decipher if this is a feature unique to humans or if it is evolutionary conserved among species, we have compared the promoter of IFNL4 from different species. IFNL4 genes can be found in most mammals except murines (mice and rats) and so we chose to compare the IFNL4 promoter from human, pig and sheep as their IFNL loci is more or less fully sequenced and genetic material could easily be obtained from tissues or cell cultures. We cloned the IFNL4 promoter as well as the IFNL2/3 promoter from these three species and placed it in front of a firefly luciferase gene to allow for easy quantification of promoter activity. Our results show that the IFNL4 promoter behaves rather different than the IFNL2/3 promoters and appears not to be stimulated by the same stimuli that readily stimulates the latter. Furthermore we find that this feature is conserved among all three species investigated.