Objective To explore effects of proliferating cell nuclear antigen (PCNA)and c-Fos protein on the early and middle embryonic development of the human spinal cord. Methods Using immunohistochemical method, the expression of PCNA and c-Fos were investigated in the central canal, anterior horn and posterior horn of spinal cord of 16 human embryos aged at the second to fourth month of gestation. Results At the second month of gestation, there were the positive PCNA immunohistochemical reaction in the central canal and alar plate of the spinal cord, but not in the basal plate. The c-Fos immunohistochemical positive reaction were localized in the epithelial cells of the central canal, alar plate and basal plate of the spinal cord. Following growth, the positive immunohistochemical staining for PCNA was also found in the epithelial cells of the central canal, anterior horn, and posterior horn of the spinal cord. The average intensity and cell number of the c-Fos immunohistochemical positive profiles decreased first, and then increased in spinal cord anterior horn (EM>P /EM><0.01), but no changes was found in the posterior horn of the spinal cord. Conclusion PCNA and c-Fos proteins may regulate the growth and development of the neuroepithelial cells of the neural tube of the human embryo.