We present a quartz crystal microbalance (QCM) immunosensor for highly sensitive detection of prostate-specific antigen (PSA) in a human serum immunoassay. In particular, in this study, we employed signal amplification using and enlarging gold nanoparticles. Because QCM measures the change of resonance frequency according to the mass change occurring on the sensor surface, we could quantitatively analyze PSA based on a tremendous increase in mass by sandwich immunoassay using AuNP-conjugated anti-PSA-detecting antibody enhanced with subsequent gold staining. The limit of detection of the PSA immunoassay in human serum without gold staining enhancement was 687 pg ml but was 48 pg ml with the gold staining-mediated signal amplification. That is, amplifying the signal resulted in increased sensitivity and reproducibility of immunoassay in a human serum.