Human epidermal growth factor (hEGF) can stimulate the division of various cell types and has potential clinical applications. Since the protein contains three intra-molecular disulfide bonds, the high expression of active hEGF in Escherichia coli has not been well researched, We fused the hEGF gene with a small ubiquitin-related modifier gene (SUMO) by synthesizing an artificial SUMO-hEGF fusion gene that was highly expressed in E. coli (DE3) strain. The optimal expression level of the soluble fusion protein, SUMO-hEGF with IPTG (Isopropyl-β-D-Thiogalactopyranoside), was up to 38.9% of the total cellular protein. The fusion protein was purified by Ni-NTA affinity chromatography and cleaved by a SUMO-specific protease to obtain the native hEGF, which was further purified by Ni-NTA affinity chromatography. The result of the reverse-phase HPLC showed that the purity of the recombinant cleaved hEGF was greater than 98%.