Aim: The ERBB gene family plays an important role in cell proliferation and differentiation, and aberrant activations could result in tumorigenesis, which makes this gene family an attractive drug target in the area of precision oncology. Materials & methods: Functional divergence analysis and conservation analysis were performed using ClustalW, MEGA7 and DIVERGE3 software. Results: One hundred and forty five functional divergence residues sites, 94 totally conserved sites and averagely 345 conserved sites of individual gene member were obtained. Some have been reported to play role in drug binding, tumorigenesis and drug resistance. Conclusion: Functional divergence residues with high posterior probabilities and conserved residues may possess certain functions, and aberrant alterations may confer drug resistance or contribute to tumorigenesis.