As a result of deep burial depth, small pore throat, poor connectivity between pores, different clay mineral contents in reservoirs, and strong reservoir sensitivity, injection wells often have problems such as rapidly increasing water-injection pressure and insufficient water-injection quantity in the process of water-injection development. The main measures used to solve the difficulties of water injection in low-permeability reservoirs include fracturing, acidizing, and surfactant depressurization and injection increase, all of which have some disadvantages of high cost and environmental damage. In recent years, depressurization and injection-increase environment-safe bio-nano-materials have been introduced into low-permeability reservoirs and have achieved good application results in China. On the other hand, although there have been many researches on EOR (enhanced oil recovery) of nano-materials, the numerical simulation field of nano-depressurization and injection-augmenting technology is still a blank that the wettability mechanism of nano-materials and EOR nano-materials used in bio-nano-depressurization and injection-augmenting technology are almost completely opposite, and the influence of adsorption on formation is almost completely opposite. The adsorption of nanoparticles in other EOR studies will reduce the porosity and make the reservoir more hydrophilic. Nanoparticles used in biological nano-technology will produce hydrophobic film near the well, which will reduce the seepage resistance through the slip of water phase. In this study, a set of water flooding model of numerical simulation technology for depressurization and injection-augmenting of biological nano-materials considering adsorption characteristics and reservoir physical properties was established, the sensitivity analysis of key injection parameters was carried out, and the application effect prediction chart of biological nano-technology was drawn, and the model and prediction chart were verified by real oilfield data. As far as we know, this is the first numerical simulation study on biological nano-technology that has been applied in oil fields.