Single-strand oligo-DNA-modified Au nanoparticles (AuNPs) undergo aggregation in the presence of poly(L-lysine) (PLL), which is attributed to the interactions between the oligo-DNA and PLL. These interactions between the oligo-DNA and PLL were identified to be electrostatic when the lysine residues of PLL were positively charged and to be hydrogen bonding when the residues were deprotonated. The aggregation was promoted with an increase in the pH value at a pH level lower than the pK(a) value of PLL (pK(a) approximately 10.0) due to the gradual deprotonation of the lysine residues and thus suppressed electrostatic interactions between the positively charged lysine residues of PLL and the negatively charged backbone phosphate groups of the oligo-DNA. At pH levels higher than the pK(a) value of PLL, the aggregation was identified to be dominated by the hydrogen bonds between the bases of the oligo-DNA and the deprotonated lysine residues of PLL. This study prompts the possibility that the spectral, and thus color, change of AuNPs upon aggregation can be used as a probe to follow the interactions between oligo-DNA and polypeptides.