Vortex-induced vibration is a common fluid–structure coupling phenomenon in ocean engineering. As a nonlinear stiffness structure caused by anisotropic deformation and support gap, nonlinear spring is of great significance in the field of vortex-induced vibration. Based on the structural dynamics equations and the wake oscillator model, the vibration model of the 2-Degree of Freedom cylinder system with the nonlinear stiffness spring is established. The stiffness ratio, mass ratio, and damping ratio of the cylinder system are changed, and the amplitude and frequency response are analyzed to obtain the effect of nonlinear spring on vortex-induced vibration. The results show that the cylinder system with a nonlinear stiffness spring can maintain a high vibration amplitude in a large Reynolds number range, and the smaller the mass ratio, the more significant the effect is. When m*=1.5, the amplitude of the cylinder system in a cross flow is greater than 0.6 at Re = 180 000–480 000. The energy harvesting in the vortex-induced vibration of cylinder systems with nonlinear stiffness springs is also studied. The efficiency depends on the damping ratio and Reynolds number. When the damping ratio is constant, the energy harvesting efficiency increases first and then decreases with the Reynolds number increases. When m*=1.5, the energy harvesting efficiency of the cylinder system is 19.27% with Re= 35 000 and damping ratio ξ=0.155. As a kind of renewable energy, energy harvesting in vortex-induced vibration is a potential development direction in the future energy field.