The effect of ultrasonic nanocrystal surface modification (UNSM) on the fatigue behavior of Ti6Al4V (TC4) in simulated body fluid (SBF) was investigated. UNSM with the condition of a static load of 25 N, vibration amplitude of 30 μm and 36,000 strikes per unit produced about 35 μm surface severe plastic deformation (SPD) layers on the TC4 specimens. One group was treated with a hybrid surface treatment (UNSM + TiN film). UNSM technique improves the micro hardness and the compressive residual stress. The surface roughness is increased slightly, but it can be remarkably improved by the TiN film. The fatigue strength of TC4 is improved by about 7.9% after UNSM. Though the current density of corrosion is increased and the pitting corrosion is accelerated, UNSM still improved the fatigue strength of TC4 after pre-soaking in SBF by 10.8%. Interior cracks initiate at the deformed carbide and oxide inclusions due to the ultrasonic impacts of UNSM. Corrosion products are always observed at the edge of fracture surface to both interior cracks and surface cracks. Coating a TiN film on the UNSMed surface helps to improve the whole properties of TC4 further.