With the occurrence of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, a number of well-functioning neurons need to be developed to make up for the loss of neurons and to restore the brain functions. Unfortunately, because the axons cannot regenerate well, brain function cannot be well compensated for even with the increasing number of newborn neurons, let alone the reformation of neural network. Cytoskeletal proteins play a crucial role in regeneration of axon. In this review, we summarize some cytoskeletal proteins, for instance, actin and actin-binding proteins, as well as tubulin and microtubule-associated proteins, and more importantly, their roles in the regulation of axonal regeneration in the brain. It will provide new opportunities for axonal regeneration after brain damage and will even bring new treatments to patients with neurodegenerative diseases.