The deformation mechanisms of a single crystal nickel-base superalloy with and without Ru-doped have been investigated under out-of-phase thermomechanical fatigue. The Ru-doped alloy exhibits a thermomechanical fatigue life more than twice as high compared to the Ru-free alloy and a difference in thermomechanical fatigue behavior is also displayed. Microstructure studies by scanning electron microscopy and transmission electron microscopy revealed that the deformation mechanism of the Ru-free alloy in the initial stage is the movement of dislocations in the γ matrix. In the later stage of the thermomechanical fatigue test, large amounts of twins are formed in the material, and a large number of stacking faults and dislocations are sheared into the γ' precipitates. By comparing with the Ru-free alloy, the Ru-doped alloy has a higher matrix strength due to the solid solution strengthening effect of Ru, and is also prone to different deformation mechanisms. For example, the stacking faults are formed in the initial thermomechanical fatigue cycles and remain in the matrix throughout the entire thermomechanical fatigue process. The formation of twins, on the other hand, is suppressed by Ru addition. Such effects are believed to extend the thermomechanical fatigue life effectively.