Abstract: Nanocellulose exhibits superior mechanical properties and is a renewable natural biomass material. Nanocellulose-based sequentially architected materials are expected to become a new generation of environment-friendly high-performance structural and functional materials leading sustainable development. The construction of reasonable multiscale nonlinear coupling relationship between interfacial mechanical behavior and material microstructure is pivotal to the strengthening-toughening design of nanocellulose-based materials. Recent research progress of interfacial mechanical behavior and design of nanocellulose-based sequentially architected materials was reviewed here. The interfacial hydrogen-bonding behavior, multiscale interfacial mechanics, and some design cases of interfaces and microstructures were discussed. At last, the summary and perspective of key points in this field were given. This paper would aim to provide new perspectives for the design and preparation of high-performance nanocellulose-based sequentially architected materials based on micro-nano mechanics and multiscale mechanics.