The proteins molecular design is an important method to develop new biotech drugs.The protein engineering technique has become a effective stratagem to improve variant properities of therapeutic proteins,including enhanced thermostability,bioactive specifity,targeted deliverty,decrease in immunity and improving pharmacokinetics.Numerous therapeutic proteins produced by protein engineering has been developed and used in clinic,asparaginase and calcitonin by site directed mutagenesis,PEGIFN α2b,γpAHirudin,pro(pro)GHRHGlyGlyCys and proproPTHGlygly has been designed and developed sucessfully in our Lab.Sitedirected mutagenesis,DNA suffling,directed evolution,expression of fusion proteins promote the creation of new therpeutic proteins,tends on rational design and engineering of therapeutic proteins were discussed.