The bovine embryonic signal interferon-τ (IFN-τ) produced by the trophoblast is known to pass through the uterine fluid towards the endometrium and further into the maternal blood, where IFN-τ induces specific expression of interferon-stimulated gene expression (ISG), for example in peripheral leucocytes. In sheep, it was shown experimentally by administration of IFN-τ that ISG is also detectable in the liver. The objective was to test whether ISG can be detected in liver biopsy specimens from Holstein-Friesian heifers during early pregnancy. Liver biopsies were taken on day 18 from pregnant and non-pregnant heifers (n = 19), and the interferon-stimulated protein 15 kDa (ISG-15) and myxovirus-resistance protein-1 (MX-1) gene expression was detected. The expression of both MX-1 (p: 24.33 ± 7.40 vs np: 9.00 ± 4.02) and ISG-15 (p: 43.73 ± 23.22 vs 7.83 ± 3.63) was higher in pregnant compared to non-pregnant heifers (p < 0.05). In conclusion, pregnancy induced ISG-15 and MX-1 gene expression in the liver already at day 18 in cattle.