A series of wholly soy-based semi-interpenetrating polymer networks (semi-IPN) have been successfully prepared from soy-oil-polyol-based polyurethane (S-PU) and modified soy protein isolate (M-SPI). Morphology, structure and miscibility of the semi-IPN films have been investigated by Fourier transform infrared (FT-IR) spectroscopy, film density, scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and ultraviolet visible (UV-vis) spectroscopy. The results show that the hydrogen bonds existing between S-PU chains are partially destroyed during the loading of M-SPI. In addition, the measured density of semi-IPN films are higher than the theoretically values, indicating the penetration of M-SPI into S-PU networks to bind intimately. Good miscibility between S-PU and M-SPI is confirmed by the single T-g observed in DSC and the high light transmittance under low M-SPI content (<20 wt %). Furthermore, DSC and DMTA results reveal that phase separation between S-PU and M-SPI in the films occurred when M-SPI content ranges from 20 to 80 wt %. After extraction of the M-SPI with tetrahydrofuran from semi-IPN, the morphology, structure and domain size of the films could be clearly observed by SEM. The mechanical properties of the semi-IPN films are investigated by tensile testing. The tensile strength of the films enhances from 7.5 to 31 MPa, while the breaking elongation recedes from 228% to 20% with the increase of M-SPI content from 0 to 80 wt %.