This paper proposes a generalized proportional integral observer (GPIO) based nonlinear predictive control (NPC) for an interior permanent magnet synchronous motor (IPMSM) to improve the flux-weakening (FW) current control performance against the complex nonlinear cross-coupling terms and the IPMSM parameters’ variations. First, the IPMSM is remodeled to further analyze the FW control difficulties caused by such cross-coupling terms and parameters variations. Considering the parameters’ variations as a kind of disturbance, a GPIO is then designed to compensate for such disturbance. A GPIO-based NPC is finally designed to handle the nonlinear cross-coupling terms to obtain an optimized current control performance. Experiments on a digital signal processor (DSP) based IPMSM servo system validate the workability of the proposed control scheme.