Objective:To mutate the codons which code the lysine at loci ? 99 ,? 82 in human hemoglobin gene to the codons which code the cystein.Methods:The objective gene to be mutated was cloned into pAlter Ex2 plasmis and then was mutated with the site directed mutagenesis mediated by oligonucleotide.Results:The sequencing of clones obtained by preliminary screening showed that the anticipated results were reached without any unexpected mutation.Conclusion:The results lay a foundation for the further development of research on expression and purification of recombinated mutant human hemoglobin gene.