Abstract: Epidermal growth factor receptor（EGFR） is a member of the tyrosine kinase receptor family. EGFR plays an important role in cell proliferation, growth and apoptosis, and regulates mammalian mammary gland development and lactation. However, there are few reports on the sequence characteristics and tissue expression of sheep EGFR gene. Small-tailed Han sheep with high milk yield（peak lactation period and empty period） and Gansu alpine fine wool sheep with low milk yield（peak lactation period） were used in this experiment. The intact CDS region of sheep EGFR gene was obtained by RT-PCR, cloning and sequencing. The structural characteristics and physicochemical properties of EGFR protein were analyzed. RT-qPCR was used to detect the expression of EGFR gene in tissues.The results showed that the CDS region of sheep EGFR gene was 3 627 bp, encoding 1 208 amino acids. The amino acid sequence of sheep EGFR was conserved among different species, it had the highest amino acid sequence homology with cattle EGFR. EGFR was a transmembrane protein with 111 phosphorylation sites. The secondary structure of EGFR was mainly composed of α-helix and random coil. String analysis showed that EGFR protein interacted with heparin-binding epidermal growth factor（HB-EGF）, epiregulin（EREG）, amphiregulin（AREG） and growth factor receptor binding protein 2（GRB2）. The EGFR was mainly showed in MAPK, PI3 K/AKT, JAK/STAT and Wnt signaling pathways, which participated in the regulation of animal mammary gland development and lactation. RT-qPCR results showed that the expression of EGFR gene was tissue-specific, space-time specific and breed-specific. The gene was expressed in the 8 tissues studied, but showed higher eexpression in kidney, ovary, liver, mammary gland and lungs. In the mammary gland tissue of Small Tail Han sheep, the expression of EGFR gene in the empty period was significantly higher than that in the peak of lactation（P＜0.05）. In the mammary gland tissue at the peak of lactation, the expression of EGFR gene in small-tailed Han sheep was higher than that in Gansu alpine fine-wool sheep. This study provided basic data for in-depth study of the lactational biological function of the sheep EGFR gene.