Gold nanoparticles were used as mass amplifiers to improve the frequency signal of QCM detection of DNA. Indirect labelling and direct labelling of DNA probes with gold nanoparticles was studied. Two-times amplification of gold nanoparticles was carried out to further improve the detection signal. It was suggested that the frequency shift of the indirect-labelling method was much more significant than that of the direct-labelling method. The detection limit of one-time amplification and two-times amplification detection of a 33-base oligonucleotide was 100 and 10 fM, respectively. Under corresponding sensitivity, the one-base mismatched DNA and complementary DNA could be distinguished clearly. As an example, the two-times amplification detection of 677TT gene type validated that the ratio of frequency shift for a complementary DNA: one-base-mismatched one was 2.1:1 under the detection limit of 10 fM.