In this study the fatigue mesoscopic elasto-plastic properties of nickel-base superalloy GH4145/SQ were investigated using the instrumented microindentation testing coupled with the analytic calculation. The indentation characteristic parameters of low-cycle fatigue specimens, such as the indentation curvature (C), the maximum penetration depth (h max ), the initial unloading slope (S), the residual depth of penetration (h r ), the recovered elastic work (W e ) and the residual plastic work (W p ), were determined from the experimental load–penetration depth (P–h) curves, and the fatigue mesoscopic elasto-plastic properties (E, σ y and n) were estimated using a well-developed analysis algorithm proposed by Dao et al. The distribution patterns of the fatigue mesoscopic mechanical properties were further verified in a statistical sense. The dependence of the fatigue mesoscopic elasto-plastic properties upon the imposed strain amplitude was discussed preliminarily in terms of microstructural examinations of fatigue failure specimens.