Human brain is located inside the skull and protected by cerebrospinal fluid. Nearly 80% of our brain consists of water, which makes our brain the most vulnerable part of our body, and injuries to brain are often fatal or lead to permanent disabilities. As a result, the characterization of mechanical properties of brain tissue becomes a must for the development of protective devices, medical diagnoses and formulation of surgery plan. To achieve the accurate characterization, the minor invasive cutting of soft tissue specimen is the prerequisite. However, both the fracture strength and equivalent elastic moduli of brain tissue are typically in the range of 0.1–10 kPa. This indicates the mechanical properties of the cut specimens may be affected by the cutting process due to the intrinsic soft nature of the brain tissue, which may readily experience large deformation and damage. Nevertheless, little is known on the damage to soft tissue incurred by the cutting process and a theoretical study about the mechanical response of the brain tissue in cutting is still lacking. In this communication, the quasi-static tensile test was first conducted to obtain the tensile strength of brain tissue. By fitting the experimental stress relaxation curves, the five-parameter constitutive model was established. In response to the lack of failure model for viscoelastic materials in ABAQUS/Explicit, the five-parameter viscoelasticity property and the failure criterion of equivalent Mises stress were then imbedded into the ABAQUS software by writing our own VUMAT subprogram to implement the numerical simulation of the cutting process of brain tissue and unveil the mechanical mechanism of the cutting process. Finally, the effects of friction coefficients between the brain tissue and the cutter, the radius of curvature of the blade, the included angle of the blade and the cutting speed on the incision force and incision displacement were discussed. With the increase of friction coefficient, the frictional force between the brain tissue and the cutter will increase and the relative slip will decrease, resulting in the increase of incision force and incision displacement. The reduction in the radius of curvature of the blade will cause the considerable drop of incision force and incision displacement in that smaller radius of curvature leads to the smaller contact area and higher stress concentration, which makes the brain tissue fail upon relative small incision force and incision displacement. The increase in the included angle of the blade will incur the increasing contact area between the brain tissue and the cutter, giving rise to increasing incision force and displacement. In contrast, the increase in cutting speed brings about the decrease of incision force and incision displacement, which can be ascribed to the reduction of localized elastic modulus of brain tissue in the cutting area. In the scale of variables investigated, the radius of curvature of the blade demonstrates more pronounced influence with respect to the friction coefficient, the included angle of the blade, and the cutting speed. It is likely that the obtained results can provide referential information for the numerical simulation of the cutting process of soft matter and the minor invasive cutting of brain tissue specimens for mechanical property measurements.