The present study demonstrated that the p53-expressing HOS osteosarcoma cells presented a significantly diminished viability when subjected to high concentrations of 7 nm (10 ppm and 5 ppm) and 60 nM (10 ppm) AgNPs, thus suggesting that p53 does play a role in AgNP-mediated cytotoxicity. This evidence concerns the gene TP53 and osteosarcoma.