PLA and TPU are two kinds of biocompatible materials, which have potential application in tissue engineering scaffolds. In order to induce the cells to proliferate and grow, and thus form 3D biological tissue, the pores of the scaffold must be opened to form interconnected porous structure. By using supercritical carbon dioxide (SC-CO2) as physical foaming agent, open-cell PLA/TPU blend foams were prepared. The cell structure, cell size, foam density and the ways of cell opening were discussed and explained by combining the rheological behavior and the morphology of the blends. The cellular structures of PLA/TPU blend foams were very different from pure PLA and TPU foams. Both 80/20 and 20/80 PLA/TPU blend foams displayed more open-cellular structures than pure PLA and TPU, which was attributed to the “sea-island” phase morphology of the blends and the difference in the storage modulus and complex viscosity of the PLA and TPU. The storage modulus of TPU was higher than that of PLA, which resulted in the cell size in PLA phase is larger than in TPU phase. When the lager cells in PLA phase contacted with the smaller cells in TPU phase, the difference of melt strength between TPU and PLA would lead to the formation of open-cell structure. It was also found that the foam density of 20/80 PLA/TPU blend foam was higher than that of 80/20 PLA/TPU blend foam, which was attributed to the storage modulus of 20/80 PLA/TPU is higher.