This　work　studied　the　relationship　between　the　fatigue　behavior　and　microstructural　evolution　of　a　second-generation　nickel-based　single-crystal　superalloy　with　[001],　[102],　and　[314]　orientations　at　room　temperature.　Strain-controlled　low-cycle　fatigue　experiments　were　executed　using　an　in-situ　Scanning　electron　microscope　(SEM)　fatigue　test　system.　Digital　image　correlation　(DIC)　mapping　combined　with　SEM　images　were　used　to　identify　strain　concentration　and　predict　areas　of　crack　initiation.　Results　showed　that　the　deformation　of　specimens　with　different　orientations　was　dominated　by　planar　slip　and　followed　Schmid　law.　Cross-slips　were　observed　in　the　specimen　with　the　[001]　oriented　orientation,　while　a　single　slip　was　observed　for　the　other　two　orientations.　Fatigue　crack　propagation　was　dominated　by　one　slip　system　in　the　[001]　and　[314]　oriented　specimens.　While　in　the　[102]　oriented　specimen,　it　was　alternately　dominated　by　two　slip　systems.　The　fatigue　life　of　Nickel-based　single-crystal　superalloys　(NBSCs)　had　a　high　orientation　dependence,　and　was　related　to　the　elastic　modulus　and　crack　propagation　path.　The　cyclic　softening　that　occurred　during　fatigue　was　caused　by　dislocation　motion.　©　2022　Elsevier　B.V.