The interaction of organic small molecules (OSMs) with a biological molecule is very important. In this contribution, quinone-imine dyes including Acridine Yellow (AY), Neutral Red (NR), Acridine Orange (AO), Brilliant Cresyl Blue (BCB), Thionin (TN), Azur A (AA), Azur B (AB), and Methylene Blue (MB) respectively with double strand DNA (dsDNA) and single strand DNA (ssDNA) were investigated based on the measurements of enhanced resonance light scattering (RLS) and TEM. Mechanism investigations have shown that groove binding occurs between dsDNA and these OSMs, which depends on G-C sequences of dsDNA and the volumes of OSMs. With the amplified RLS signals resulting from the interactions of OSMs with DNA, a new technique has been proposed to detect the hybridization and mismatch of DNA labeling neither the target nor the probe DNA. The results have suggested that the extent of the amplified RLS signals of dsDNA by AY is the maximum among these eight OSMs, and therefore, it has been selected as a typical model system for further discussions.