Epidermal growth factor (EGF) is a growth factor in protein structure that stimulating division, differentiation, survival, proliferation, growth and migration of the cells and is involved in many physiological and pathological processes of the organism. EGF exerts its biological effects through EGF receptor (EGFR) which is a transmembrane protein. Epidermal growth factor receptors are located on the cell surface of many tissues that include lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus, placenta, cornea and glia. EGF activates the mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 and phosphatidylinositol 3 kinase (PI3K)-Akt signaling pathways stimulating cell proliferation and survival through binding to EGFR. EGFR plays a role in proliferation and differentiation of astrocytes and survival of postmitotic neurons. EGFR is also known to have an important role in oligodendrocyte development. In acute spinal cord injury, EGF treatment alleviates the deterioration in the blood-spinal cord barrier permeability via phosphatidylinositol 3 kinase/Akt/Ras-releated C3 botulinum toxin substrate 1 (PI3K/Akt/Rac1) pathway and increases locomotor activity. Intranasal heparin-bound EGF treatment increases the formation of new oligodendrocytes from progenitor cells and induces functional recovery in newborn brain injury model. Plasma EGF levels is suggested that a biological marker of cognitive decline in patients with Parkinson disease and Alzheimer disease. EGF is evaluated as a key molecule for remyelination in patient with multiple sclerosis. EGF treatment is considered as a novel approach to the treatment of nervous system diseases. In this review, it has been aimed to present a knowledge about neuroprotective effect of EGF.