In this study, molecular dynamics simulations were used to investigate the micro-scale effects of modification of nano-SiO2 with commonly used silane coupling agents (KH550, KH560, KH570, and KH792) on the cellulose/nano-SiO2 interface. The relative optimum silane coupling agent and grafting density for nano-SiO2 modification to improve the cellulose/nano-SiO2 interface were determined. The results showed that at the same grafting density, modification of nano-SiO2 with KH792 yielded the highest interfacial binding energy and binding energy density, the largest number of hydrogen bonds at the cellulose/nano-SiO2 interface, the strongest binding to the cellulose chains, and the largest overlapping area at the cellulose/nano-SiO2 interface. We found that the non-bonding interaction energy played a decisive role in the energy of the model system and the interfacial interaction force mainly consisted of van der Waals forces and the hydrogen-bonding energy. When silane coupling agents with amino groups (KH550 and KH792) were used to modify nano-SiO2, the number of hydrogen bonds at the cellulose/nano-SiO2 interface was larger than that for unmodified nano-SiO2. When silane coupling agents without amino groups (KH560 and KH570) were used to modify nano-SiO2, the number of hydrogen bonds at the cellulose/nano-SiO2 interface was lower than the case for unmodified nano-SiO2. Nano-SiO2 modification with various amounts of KH792 was investigated. The results showed that the interfacial bonding energy increased with grafting density. When the grafting density was 1.57 nm-2, the interfacial bonding energy and number of hydrogen bonds formed at the cellulose/nano-SiO2 interface was relatively stable, which indicates that the interface had reached a relatively stable state. Modification of nano-SiO2 with KH792 achieved the greatest improvement of the cellulose/nano-SiO2 interface; this interface reached a relatively stable state when the grafting density of KH792 was 1.57 nm-2.