Objective Members of the epidermal growth factor (EGF) family of ligands and their receptors regulate migration and growth of intestinal epithelial cells: integrins, the immunoglobulin superfamily, selectins and cadherins. Each family is composed of a number of constitutional members. These cell adhesion molecules mediate the process of cellular adhesion to either the extracellular matrix (ECM) or initiate cell-cell adhesion. Focal adhesion kinase (FAK) is a major mediator of integrin signaling pathway. In this paper, the interaction between FAK and EGFR, and the regulation of FAK on the EGFR signaling pathway was studied. Methods Cell lines expressing del 1-693FAK-GFP, del 1-100FAK-GFP and FAK-GFP were used. The deletion mutants of FAK, del 1-693FAK-GFP and del 1-100FAK-GFP lost the ability to recruitment to adhesion sites. PI electrophoresis and Western blot analysis were applied. Results PI electrophoresis analysis indicated that the phosphorylation of FAK was regulated by EGF stimulation. Western blot analysis showed that expression of del 1-693FAK-GFP and del 1-100FAK-GFP inhibited the phosphorylation of MAPK. However, FAK-GFP enhanced the phosphorylation of MAPK and inhibited the phosphorylation of Akt. Conclusion The results suggested that FAK regulates the balance between MAPK and Akt signal pathways through interaction with EGFR.