Soy protein based biodegradable polyurethane (PU) foams were prepared by incorporating soy protein isolate (SPI) into flexible PU foam. The effects SPI content and isocyanate index on the density, resilience, compression set, and biodegradability of the soy protein based PU foams were investigated. The results showed that, soy protein enhanced the compression set, resilience, and biodegradability of PU foams, but increased the density. Furthermore, soy protein can increase open cell proportion in the soy protein based flexible PU foams, and then regulate their properties. The density and compression set value of the soy protein based PU foams decreased with increase in isocyanate index, while the resilience increased. The biodegradability of soy protein based flexible PU foam makes it a prospective material for disposable usage.