Bulk hybrid polymethyl methacrylate (PMMA)/SiO2 glass with Sb2S3 nanocrystals was prepared by the sol-gel process. We tried to minimize the quantity of water as much as possible in tetraethyl orthosilicate (TEOS) hydrolyzing, prepolymerized the organic monomers, mixed inorganic precursors, and prepolymerized organic monomers under a noncosolvent condition to reduce possible volume shrinkage. A silane coupling agent, which hydrolyzed simultaneously with TEOS, was introduced into the system to improve the miscibility of the organic and inorganic materials. The maximum dopant of Sb2S3 was 9 wt% in our experiments. The second-harmonic generation was observed in the hybrid PMMA/SiO2 glasses with electron-beam poling. Second-harmonic intensity increased with increase of accelerating voltage, current, and the content of Sb2S3 nanocrystals. The maximum χ2 in our study, as large as 1.64 p.m./V, was obtained under the optimized poling condition conducted at 25 kV, 20 nA, and 10 min. It was indicated from the thermally stimulated depolarization current measurements that the nonlinear layer was located in the thin 10-μm irradiated surface of the glass.