To understand the effect of pre-strain on the integrity assessment of titanium structure with crack, the dependence of tensile mechanical parameters, fracture toughness, failure assessment diagram (FAD) on pre-strain were focused. Firstly, tensile tests revealed that, the yield stress and the yield-ultimate strength ratio increased, but the ductility decreased with pre-strain value, while the fracture toughness was decreasing with pre-strain. Then, based on finite element (FE) analyses of compact tension (CT) specimen and titanium pressure vessel with crack, the plastic zone near the crack tip was decreasing with pre-strain, resulting in the decreasing of J-integral. Moreover, the failure assessment curves (FAC) of Options 1 and 3 in BS 7910: 2013 were varying with pre-strain, and the acceptable area was decreasing. Therefore, the reserve factor on yield stress increased with pre-strain, but that on fracture toughness decreased significantly. In brief, the pre-strain significantly affects the failure assessment of titanium pressure vessel with crack, and needs to be considered in the integrity assessment.