An　approach　to　protein　design　is　proposed　based　on　the　relative　entropy　and　a　reduced　amino　acid　alphabet.　In　this　approach,　the　relative　entropy　is　used　as　a　minimization　object　function.　The　method　has　been　tested　on　a　real　protein＇s　off-lattice　model　successfully,　and　the　results　are　similar　to　those　obtained　from　other　design　studies.　It　can　be　applied　as　a　uniform　frame　for　both　folding　and　inverse　folding　of　protein.　An　iterative　calculation　method　of　the　ensemble　average　of　the　contact　strength　is　proposed　at　the　same　time.