A robust nonlinear meshfree computer-aided-engineering (CAE) analysis algorithm based on the Reproducing Kernel Particle Method (RKPM) is employed for simulating the installation and sealing performance of a truck-based radiator hose/fitting/clamp system assembly. The formulation of the present nonlinear meshfree CAE simulation comprises the geometric and material nonlinearities, a Lagrangian material based reproducing kernel shape function, a pressure projection method for nearly incompressible rubber hose material, and a direct transformation method for frictional contact boundary conditions. This simulation, which defines a radiator hose/fitting operating process series as insertion, clamping, pressurization and pull-off, provides a parametric investigation on the effect of clamping depth, clamping width, clamping location, and fluid pressure load on the hose-fitting contact seal width, contact pressure distribution, and the maximum pull-off force properties. Moreover, a series of laboratory room-temperature pull-off tests at various pulling rates has been performed to validate the predictions from the meshfree CAE simulation. The value of the pull-off force predicted from the meshfree analysis is in good agreement with that measured at the pulling rate of 0.42 mm/s. Based on the finding from this investigation, a quantitative performance database on the installation and sealing characteristics of a truck-based radiator hose/fitting/clamp system assembly has been established. The advanced meshfree method can be considered as a useful tool in math-based technology for simulating other large deformation engineering problems that are difficult to deal with by the conventional finite element methods.