SH-SY5Y cells are a subclone of a neuroblastoma cell line derived from human bone marrow. With similar morphological， physiological， and biochemical characteristics to human cells， SH-SY5Y cells can be transformed into neuron-like cells， showing a range of highly instructive neurobiological characteristics. They are widely used in in vitro experimental studies of nervous system diseases， based on the advantages of simple and rapid large-scale expansion， reproducibility， and low-cost maintenance and with no ethical concerns associated with primary neuron culture. SH-SY5Y cells can be prepared into undifferentiated and differentiated forms. Through various differentiation protocols， SH-SY5Y cells can differentiate into neuron-like cells which are more approximate to mature human neurons. With different differentiation protocols， SH-SY5Y cells express different neuronal phenotypes， showing their pros and cons when applied in research on the pathophysiological mechanisms of different diseases， and they are more suitable for the studies of neurodegenerative diseases， such as Parkinson’s disease and Alzheimer’s disease. This paper reviews the neural differentiation methods of SH-SY5Y cells and their application in the experimental studies of neurodegenerative diseases.