A highly sensitive terahertz (THz) waveguide resonance biochemical sensor is designed and simulated. The sensor consists of a silicon prism, a dielectric layer and a nanoporous gold film. The nanoporous gold film acts as both a THz waveguiding layer and a biochemical molecular enrichment layer, which can enhance the interaction between the THz waveguide mode and the adsorbed biochemical molecules, consequently improving the sensor’s sensitivity. When the THz transverse electric (TE) or transverse magnetic (TM) modes are excited by the prism-coupling method, the THz absorption of the nanoporous gold film results in the sharp resonance dips in the THz reflection spectrum. The resonance frequencies of the THz waveguide modes and the sensitivity to either liquid refractive index (RI) or adsorbed molecules can be determined with the measured reflection spectra, and the sensor’s sensitivity and its figure of merit (FOM) can be improved by adjusting the thickness and RI of the dielectric layer. The simulation results at 45º incidence angle indicate that the resonance frequencies of the TE and TM modes of the sensor linearly change with increasing either liquid RI or the amount of adsorbed molecules, and the RI sensitivity and the FOM with the TM mode are 13.42 THz/RIU and 167.70/RIU, respectively. Compared with the TM mode, the TE mode has a lower sensitivity to lqiuid RI but a high sensitivity to adsorbed molecules. The reason for these differences is that with the TE mode the evanescent field penentrating out of the nanopous gold film is weaker than that with the TM mode.