Combined protein homologous modeling with analysis of electrostatic surface potential energy, mutant ricin toxin A chain, which was suggested to be bioactive, was designed. The gene of ricin toxin A chain was amplified by PCR and inserted in pKK223-3 to construct a prokaryotic expression vector, which was highly expressed in E.coli system. Moreover, the expression products showed obvious cytotoxicity, just in agreement with the prediction of modeling.