Localized surface plasmon resonance (LSPR) not only broadens the spectral response range of materials, but also enhances the local electric field so as to enhance the Raman signal of the molecule to be measured, playing an important role in the life sciences. In this paper, the model of single gold nanoparticle (AuNP) and double gold nanoparticles (AuNPs) in whole blood environment is established and the three-dimensional finite element method is used to systematically study effect of particle size, gap and whole blood extinction coefficient on near-field enhancement of AuNPs. The simulation results show that in single AuNP model of the whole blood environment, as the particle size increases, the plasmon resonance peak red-shifts, and the local electric field is the largest when the size is 80 nm. Compared with air medium, the AuNP resonance peak in whole blood medium red-shifts and the local electric field enhances. The effect of extinction coefficient of whole blood on local electric field was very small, and the difference of local electric field enhancement is less than 0.1 V/m. In the double AuNPs model of whole blood environment, as the gap between the two particles decreases, the plasmon resonance peak blue-shifts and the local electric field increases. When the distance between the two particles is 1 nm, the Raman enhancement factor can be as high as 1011. This study provides theoretical guidance for surface-enhanced Raman scattering (SERS) sensitivity testing of drug molecules and biomarkers in the whole blood environment.