Structural　optimization　has　become　an　important　tool　for　structural　designers.　It　helps　the　designers　to　find　optimal　design　solutions　with　better　exploitation　of　materials　subject　to　various　constraints.　In　this　article,　to　face　the　critical　issue　of　huge　horizontal　thrust　occurred　in　the　Calatrava　bridge　over　the　Grand　Canal　of　Venice,　single-objective　and　multi-objective　genetic　algorithm　(GA)　based　optimization　procedures　are　set　up,　and　the　thickness　optimization　of　the　bridge　is　carried　out　separately　with　the　proposed　design　procedures　and　the　optimization　module　implemented　in　ANSYS.　The　results　are　compared　in　terms　of　steel　volume　and　horizontal　thrust　level.　It　shows　that　the　GA-based　design　procedures　are　effective　tools　to　achieve　optimal　design　due　to　the　global　search　ability　of　GA.　Further,　with　these　powerful　tools,　more　reasonable　thickness　distributions　of　steel　plates　and　tubes　of　the　Calatrava　bridge　can　be　obtained,　meanwhile,　the　horizontal　thrust　can　be　reduced　remarkably,　and　hence　the　high　cost　due　to　the　large　horizontal　thrust　of　original　design　could　be　reduced.