To research whether poly-L-lysine-starch nanoparticle (PLL-StNP) could protect DNA from ultrasound damage or not, a series experiments were carried out: plasmid DNA-PLL-StNP complexes were treated with ultrasound for diverse times; the electrophoresis result proved that DNA bound to the complexes all the same. To investigate whether the conjugated DNA was completely protected or not, cDNA fragments bound to PLL-StNP were treated with ultrasound, and matched molecular beacons (MBs) were added. The cDNA-MB-PLL-StNP complexes exhibited dramatically increasing fluorescence, and had the same intensity as that of those MBs that were hybridized with free cDNA fragments. After being treated by ultrasound, the pIRGFP plasmid DNA-PLL-StNP complexes were transferred into COS-7 cells mediated by ultrasound. Green fluorescence protein expressed in most of the cells. Those results indicated that PLL-StNP could completely protect DNA from ultrasound damage. Furthermore, the DNA kept the same function as untreated one.