A　DOE　(Design　of　Experiment)　methodology　based　on　finite　element　analysis　is　presented　to　investigate　thermal　fatigue　reliability　of　multi-row　QFN　packages.　In　this　method,　the　influences　of　material　properties,　structural　geometries　and　temperature　cycling　profiles　on　thermal　fatigue　reliability　are　evaluated,　a　L27(38)　orthogonal　array　is　built　based　on　Taguchi　method　to　figure　out　optimized　factor　combination　design　for　promoting　thermal　fatigue　reliability.　Anand　constitutive　model　is　adopted　to　describe　the　viscoplastic　behavior　of　lead-free　solder　Sn3.0Ag0.5Cu.　The　stress　and　strain　in　solder　joints　under　temperature　cycling　are　studied　by　3D　finite　element　model.　The　modified　Coffin-Manson　model　is　employed　to　predict　the　fatigue　life　of　solder　joints.　Results　indicate　that　CTE　of　PCB　board,　the　height　of　solder　joint　and　CTE　of　epoxy　molding　compound　have　critical　influence　on　thermal　fatigue　life　of　solder　joints.　The　fatigue　life　of　multi-row　QFN　package　with　original　design　is　767　cycles,　which　can　be　substantially　improved　by　5.43　times　to　4165　cycles　after　optimized　factor　combination　design.