The　cable-stayed　bridges　(CSBs)　with　high-low　towers　have　obvious　asymmetry　in　structural　layout　and　mechanical　behavior.　The　stiffness　and　vibration　mode　of　CSBs　with　high-low　towers　are　obviously　different.　In　order　to　optimize　the　mechanical　performance　of　CSBs　with　high-low　towers,　taking　the　Shunxing　Bridge　with　the　main　span　of　626　m　as　example,　a　design　optimization　study　is　carried　out　from　the　suitable　structural　system,　the　ratio　of　side　span　to　main　span,　and　the　setting　of　auxiliary　piers.　The　results　show　that　temperature　load　is　a　key　factor　in　determining　the　unconsolidated　system　of　the　CSB　with　high-low　towers,　and　it　is　also　related　to　the　height　of　the　lower　pylon.　A　reasonable　ratio　of　side　span　to　main　span　can　decrease　the　static　and　dynamic　response　of　the　CSB　with　high-low　towers;　The　setting　of　auxiliary　pier　can　increase　the　structural　rigidity　and　greatly　reduce　the　stress　and　vertical　deformation　of　the　main　beam　on　the　side　span.　The　research　results　can　provide　reference　for　the　design　of　long-span　CSB　with　high-low　pylons.　©　2023　The　Authors.