Poly-L-lysine-modified silica nanoparticles (PMS-NP) is a novel nonviral vector for gene delivery, which can efficiently deliver plasmid DNA and antisense oligonucleotides into cultured cells in vitro in the presence of serum-free medium. However, little is known about whether PMS-NP is a suitable carrier for gene delivery by oral administration. To this end, oral gene delivery assays were performed, and glucose transporting tests showed that PMS-NP had no obvious toxicity to intestine of BALB/C mice. Efficient reporter gene expression was detected in stomach and intestine where expression was mainly observed in mucous membrane cells. These results indicated that PMS-NP was a low-toxicity carrier, hence demonstrating its potential for fundamental research and gene therapy, especially for oral gene therapy.