A refractive index (RI) tunable polysiloxane coating was fabricated based on the cross-linked network structure embedded with mesoporous silica nanoparticles (MSNs), in which the MSNs were utilized to modulate the RI as well as to support the interior structure of the polysiloxane coating. The Si–O–Si inorganic backbone structure in combination with characteristics from the photopolymerization of active bonds produced the main cross-linked network structure, and controllable embedding of MSNs constructed the network-sphere structure. This approach eliminated the high-temperature post-treatment that was needed to remove the template, which ensures the safe application for temperature-sensitive laser crystal substrates and avoids coating structure collapse. In addition, degradation of the resulting coating can be minimized due to the similar chemical formation between MSN and polysiloxane coating. Hereby, a polysiloxane coating with expected spectral and laser damage-resistant properties can be obtained. This will facilitate the fabrication and application of a laser component with both high-transmission and high-flux capability for a high-power laser system.