The potentiality of surface-enhanced Raman scattering (SERS) to detect ultralow concentrations of analyte has attracted much attention in detection of trace components in both medicinal and environmental samples. However, detection at trace concentration usually requires sophisticated systems. Here, we present an ultrasensitive and facile SERS approach, a two-step centrifugation method, which achieved a detection limit of 500 fM with phenformin hydrochloride and risperidone as acidic and alkaline analyte, respectively. This method consists of two steps: (1) centrifuging colloidal silver to increase nanoparticles' concentration and to remove small-size nanoparticles, thus increasing the chance of analyte adsorption on large nanoparticles that have strong SERS activity; (2) centrifuging samples after the analytes were mixed with nanoparticles. After the first centrifugation and mixing with aqueous analyte, the colloidal silver is either flocculated (for high-concentration samples) or forms a nanoparticle-analyte complex (for low-concentration samples). Until the second centrifugation, the concentration of analyte and hot-spot formation is significantly increased, and thus a high SERS enhancement factor is obtained. In short, the two-step centrifugation method overcomes drawbacks of the traditional method, which demands not only sophisticated operation but also expensive instruments, to fully exploit the potential of SERS detection.