2E12 is a new aluminum alloy material made in China. It is to be used in aircraft fuselage skin structure. Damage tolerance performance is one of its key indicators for the material. According to the requirement of damage tolerance design， this paper designs three typical test pieces of fuselage panel structure， including single-span crack， double-span crack and crack repair. Firstly， the numerical analysis of crack propagation and residual strength is completed， and then the verification test is carried out. The results are compared with those of 2024 aluminum alloy. The results show that the damage tolerance of 2E12 aluminum alloy material can meet the design requirements. Compared with single crack propagation， the existence of multi-crack increases the crack growth rate significantly， and the total life of multi-cracks is shortened by about 30%.The error of crack propagation analysis and test results is less than 10%. The residual strengths of all test pieces are in good agreement， and the difference between the analytical results and the experimental results is about 2.3%.