In small-batch and complex product assembly, manual assembly is irreplaceable because of human flexibility and adaptability. It is a research focus in the field of intelligent manufacturing to improve assembly efficiency by using intelligent means to assist manual assembly. However, the newly added equipment brings additional learning cost and operational complexity to the assembly personnel, which makes it difficult for the assembly personnel to truly and naturally integrate into the intelligent manufacturing scene. Therefore, the friendly and natural human–robot collaboration mechanism is studied in the area of human-centered manufacturing research. To address this issue, an assembly digital twin framework is introduced in this chapter, to enable the proposed marker-less and view-free natural assembly registration method, the operation history-based assembly progress tracking method, and the proactive simulation-driven part installation guidance method. In the constructed digital twin-enabled assistance scene, automatically intelligent suggestions are provided based on the human vision, operation, and intention, thus realizing the human-centered assembly.