In-line and cross-flow vortex-induced vibration (VIV) of flexible cylinders is studied based on the VIV experiment. The relationship of two-degree-of-freedom of vortex-induced vibration of flexible cylinders is also investigated. A nonlinear model, with fluid-structure interaction, of two-degree-of-freedom VIV of flexible cylinders is then proposed. It is shown that the ratio of the frequencies and amplitudes of in-line and cross flow VIV of the cylinders changes with current velocity/Reynolds number. The ratio of the VIV frequencies is 1.0 beyond the lock in district and 2.0 within the lock in district, respectively. And the ratio of the VIV amplitudes is 1.0 beyond the lock in district and 1/3 to 2/3 within the lock in district.