The epidermal growth factor (EGF) superfamily includes the protein 6 with an epidermal growth factor-like protein (EGFL6). EGFL6 has a signal peptide domain with an amino terminus and a MAM domain with a carboxy terminus. There are four whole EGF-like repeat regions and one partial EGF-like repeat region. Three of these regions include calcium-binding structures and an arg-gly-asp (RGD) integrin interaction motif. The epidermal growth factor-like (EGFL) and EGF domains have identical amino acid residues. Cell division, differentiation, mortality, cell adhesion, and migration are all affected by EGFL6. EGFL proteins are involved in a broad range of biological activities, making it important in tumor development and angiogenesis. We highlighted the latest development of EGFL6 research on tumor proliferation, invasion, and migration in this review.