The work aims to strengthen TC4 titanium alloy with small hole by laser shock peening (LSP) to improve its fatigue life, because the fatigue fracture of the TC4 titanium alloy hole used in the key bearing lugs is a difficult problem affecting the flight safety of the aircraft. FEM numerical simulation of TC4 titanium alloy samples with small hole subjected to single point LSP with or without filler and multi-point lapping LSP was carried out to determine the optimal LSP technology and design double-hole fatigue sample to conduct fatigue test. The effective range of single spot LSP with a diameter of 3 mm was only 1.9 mm. When the hole was filled and the center of the innermost ring laser spot was 0.75 mm away from the edge of the hole, the residual stress field on the surface near the hole was uniformly induced by single spot LSP, and no tensile residual stress was introduced. The value of compressive residual stress of the first strengthened plane was slightly higher than that of the latter strengthened plane, and the uniformity of the stress field of multipoint LSP on the hole edge under 46.5% radial lapping rate was better than 36.5% and 56.5% radial lapping rate. The fatigue life of the sample was improved after LSP, and the strengthening effect dramatically increased with the decrease of the maximum load. The fracture analysis showed that the crack source at the edge of the hole moved toward depth direction after LSP and the distance between the fatigue bands in the crack growth zone decreased significantly. The optimal LSP technology is 56.5% circumferential lapping ratio, 46.5% radial lapping ratio, distance of 0.75 mm between the center of the innermost laser spot and the edge of the hole and the hole filled with filler subjected to both sides LSP at the same time. LSP introduces a compressive residual stress within 600~800 MPa on the surface near the hole, and the fatigue life of the simulated sample increases by 6.98%~ 60.96%.