One of the main goals of bone tissue engineering is to develop suitable bio-acceptable materials for bone graft substitutes, especially for filling large defects. In the present study, porous poly(lactic-co-glycolic acid) (PLGA)-silica scaffolds were successfully fabricated using indirect microstereolithography technology. The scaffolds were evaluated in vitro by analyzing their microscopic structure, porosity, and stiffness. Following in vitro osteogenic induction, human adipose-derived stromal cells (ADSCs) were seeded in the scaffolds, and the expression levels of osteocalcin mRNA and collagen type I protein were detected by RT-PCR and Western blotting, respectively. We further evaluated the osteoinductive efficacy of the scaffolds in vivo by implanting human ADSC-seeded scaffolds into athymic mice. The silica particles improved the mechanical strength of PLGA scaffolds, and the PLGA-silica scaffolds exhibited better osteogenic potential in vitro than conventional PLGA scaffolds. The in vivo osteogenic events after scaffold implantation were consistent with those observed in vitro. This study demonstrates the potential of PLGA-silica scaffolds seeded with human ADSCs as a useful tool for bone tissue engineering.