In-situ observation of crack growth and electron backscatter diffraction observation of microstructure around artificial surface defect and at mated crack surfaces are conducted for very high cycle fatigue (VHCF) of TC17 alloy. The artificial surface defect induced VHCF failure presents no slow process of crack initiation and early growth accompanied with nanograin formation commonly observed for internal cracking induced VHCF. It is attributed to the synergistic effect of cyclic stress with time dependent process (e.g. the influence of moisture, action of hydrogen, etc.). The nanograins and deformation twins are also observed in some alpha grains at or near crack surfaces.