Vortex-induced vibration (VIV) of a stay cable subjected to a wind profile is numerically simulated through combining computational fluid dynamics (CFD) code CFX 10.0 and computational structural dynamics (CSD) code ANSYS 10.0. A stay cable with the inclined angle of 30° is used as the numerical model. Under a profile of mean wind speed, unsteady aerodynamic lift coefficients of the cable have been analyzed in both time domain and frequency domain when VIV occurs. The results indicate that the lift coefficient wave response of the stay cable under a wind profile is different from that of an infinitely long cable under a uniform flow in water (i.e., without consideration of profile) obtained by direct numerical simulation. Cable oscillations can severely affect the unsteady aerodynamic frequencies, change flow field distribution near the cable and affect the vortex shedding in the wake.