In order to achieve accurate prediction of low cycle fatigue life of nickel-based single crystal superalloy DD6 after shot peening, low cycle fatigue experiments on DD6 round bar parts after shot peening were carried out, and the mechanism of the effect of shot peening on fatigue life of single crystal superalloy was analyzed. On this basis, a finite element model of the shot peening process for anisotropic materials was established to obtain the residual stress distribution and roughness due to shot peening. Based on the damage mechanics of continuous media, the low cycle fatigue life prediction model of shot peening nickel-based single crystal superalloy DD6 was established considering the influence of residual stress and roughness on the low cycle fatigue life, which was used to predict the low cycle fatigue experiment results. The surface roughness of the specimens increased after shot peening, and the average surface roughness after shot peening was 5.10 times of that before shot peening. The original matrix phase of DD6 single crystal alloy before shot peening was good, and the strengthened phase showed a good cubic structure; however, the boundary of the two phases gradually disappeared after shot peening due to the violent plastic deformation of the specimen surface. The low cycle fatigue life of DD6 single crystal alloy under different loads was improved after shot peening, and the maximum increase was 108%. The residual stress relaxation in the high-temperature environment caused the peening effect to be inversely proportional to the experiment temperature. Due to the effect of residual stress, most of the fatigue cracks initiated on the subsurface of the specimens, while a few initiated at the location of deeper craters on the surface. Considering that the single crystal alloys are anisotropic materials, Hill anisotropic yielding criterion was used to simulate the process of the single crystal superalloy shot peening. The finite element simulation of the shot peening process yielded residual stress distribution in a region 130 μm deep on the surface of the specimen. The surface residual stress was ?380.16 MPa, and the maximum residual compressive stress was located at the depth of 41.9 μm, reaching ?780.46 MPa. The stress concentration factor was calculated as 1.193 by equating the uneven craters to semicircular notches. The residual stress introduced by the eigenstrain method in the finite element model was generally the same as the simulation result. The residual stress mainly affected the stress conditions in the surface layer of the specimens, resulting in an about 10% decrease of the surface octahedral Schmid stress amplitude. The DD6 low-cycle fatigue experiment results were within twice of the predicted life. Conclusions indicate that the shot peening can effectively improve the low cycle fatigue life of DD6, and the mechanism of influence on the low cycle fatigue life is the introduction of residual stress and the change of roughness. The finite element model can accurately simulate the single crystal alloy shot peening process. The developed model for predicting the low-cycle fatigue life of shot peening nickel-based single crystal superalloy DD6 has good accuracy.