In the pharmaceutical industry, nano-size materials are designed as drug carriers and diagnosis probes. Interactions between nano-size materials and chemicals need investigating. Here, we investigated whether nano-size materials affect chemical-induced toxicity using silica particles, which have been widely used in cosmetics and drug delivery and have diameters of 70 (SP70), 300 (SP300) and 1000 (SP1000) nm, a popular anti-tumor agent, cisplatin, and a widely used herbicide, paraquat. Mice were treated with either cisplatin (100 micromol/kg, intraperitoneally) or paraquat (50 mg/kg, intraperitoneally), with or without intravenous silica particle administration. All treatments were non-lethal and did not show severe toxicity, except for injection with both cisplatin and SP70, which were lethal. When mice received with paraquat and/or the silica particles, synergistic enhanced toxicity was observed in both paraquat- and SP70-treated mice. These synergic effects were not observed with either Si300 or 1000 treatment. Our findings suggest that further evaluation on the interaction between nano-size materials and chemicals is critical for the pharmaceutical application of nanotechnology.