The fact that proteins and small molecules in biological systems have vibrational frequencies in the terahertz (THz) spectrum (0.3–100 THz) range, comparable to the energy of weak molecular interactions such as hydrogen bonds and π-π stacking, suggests that terahertz radiation may modulate biological functions through resonance. Using the IL-12/receptor complex as a model, this study combined molecular dynamics simulations and free energy calculations to investigate the impact of THz waves on the affinity between the key residue LYS192 of the IL-12p35 subunit and the receptor binding site GLU117. The results demonstrated that 42.96 THz waves inspire C-O bond vibrations in GLU117, inducing a shortening of hydrogen bond lengths (N-H \(\cdots\) O) and significantly enhancing inter-residue interactions. Under the influence of terahertz radiation, the binding free energy of the IL-12/receptor complex decreased by 114.4 kJ/mol, confirming the specific promotion of ligand-receptor binding at this frequency. This work innovatively proposed a THz-targeted immune modulation strategy, offering a novel approach to overcome the toxicity limitations of IL-12 therapies. With its non-invasive character (compared to traditional agonists), it shows great potential for use in immunotherapy.