Motivated by the need to decrease initial contact seal stress on Nd:glass coated with SiO2 sol–gel film and effectively control the surface contaminants from film debris induced by stress in the assembly process, a novel vacuum clamping method is studied to achieve the purpose of low stress and low contamination. In this article, theoretical analyses, numerical simulations, and field experiments are used to verify the feasibility of this method. Mechanical simulation results indicate that under the same radial compression conditions, the higher the hollowness of the O-ring rubber, the less the contact stress on Nd:glass. In addition, microstructures of the SiO2 sol–gel film are observed by scanning electron microscopy, and the damage mechanism is analyzed in order to optimize assembly stress. By optimizing the distribution of hollowness, the honeycomb structure is proved to have lower contact stress due to its larger deformation. Finally, experimental results verify that the low-stress vacuum clamping method can meet the strict surface cleanliness requirements of Nd:glass. This study also provides a promising method for clean assembly of other large-aperture optics.