In　this　paper,　a　life　prediction　method　based　on　damage　mechanism　for　titanium　alloy　TC4　under　multiaxial　thermo-mechanical　fatigue　loading　is　proposed.　Temperature　and　time　dependent　influence　factors　are　proposed　and　introduced　into　the　strain　amplitude-life　curve　method　to　consider　the　temperature　and　time　dependence　of　damage,　respectively.　The　increase　in　fatigue　and　oxidation　damages　caused　by　tensile　mean　stress　and　non-proportional　additional　hardening　is　expressed　by　the　mean　stress　in　Macaulay　brackets　and　by　using　a　multiaxial　damage　parameter,　respectively.　A　fast　cracking　influence　factor　is　proposed　to　consider　the　influence　of　fast　cracking　of　materials　caused　by　the　combined　action　of　high　temperature,　tensile　stress　and　shear　stress　on　damage　behavior.　The　material　constants　are　identified　by　test　data　under　uniaxial　and　proportional　loadings,　and　are　further　used　for　prediction　under　non-proportional　loading.　The　failure　life　results　of　uniaxial　isothermal　fatigue　tests　with　and　without　dwell　time,　uniaxial　and　multiaxial　thermo-mechanical　fatigue　tests　are　used　to　verify　the　proposed　method.　The　value　of　the　scatter　band　of　life　prediction　result　is　less　than　±　2,　as　well　as　the　maximum　and　mean　relative　errors　between　predicted　and　experimental　strain　amplitudes　are　18.49%　and　6.54%,　respectively.　©　2023　Elsevier　Ltd