Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2), is a transcription factor that interacts with NF90 to regulate gene expression. It has long been implicated in the regulation of cell proliferation. However, the role of NF45 in the process of peripheral nervous system regeneration after injury remains poorly understood. Herein, we investigated the spatiotemporal expression of NF45 in a rat sciatic nerve crush model. We detected the up-regulated expression of NF45 in Schwann cell after sciatic nerve crush. What's more, the expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA) exhibited a similar tendency with that of NF45. In cell cultures, we observed increased expression of NF45 during the process of TNF-α-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of NF45 led to enhanced expression of p21 and also impaired proliferation of Schwan cells. Taken together, our data implicated that NF45 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cell.