The　fatigue　damage　behavior　was　experimentally　investigated　in　different　axial-torsional　thermo-mechanical　loading　conditions　for　Ni-based　superalloy　GH4169.　The　strain　controlled　tests　were　carried　out　with　the　same　von　Mises　equivalent　mechanical　strain　amplitude　of　0.8%　in　the　temperature　range　from　360　degrees　C　to　650　degrees　C.　The　results　show　that　the　fatigue　life　is　drastically　reduced　when　the　axial　mechanical　strain　and　the　temperature　are　in-phase,　which　can　be　due　to　that　the　creep　damage　is　induced　by　the　tensile　stress　at　high　temperature.　Moreover,　the　fatigue　life　is　further　decreased　when　the　axial　mechanical　strain　and　the　shear　strain　are　out-of-phase,　which　can　be　attributed　to　that　the　non-proportional　hardening　can　increase　the　creep　and　the　oxidation　damages.　Furthermore,　the　tensile　stress　is　crucial　to　the　nucleation　of　creep　cavities　at　high　temperature　compared　with　the　shear　stress.　The　tensile　and　shear　stresses　all　can　increase　the　creep　damage　under　fatigue　loading　at　high　temperature.　In　addition,　the　oxidation　damage　can　be　induced　during　cyclic　loading　at　high　temperature,　and　it　can　be　increased　by　the　tensile　mean　stress　caused　in　non-isothermal　loading.