Abstract: Due to the prolonged duration of low-frequency radiation and the fine structures of multi-conductor transmission lines (MTLs), the time-domain field-to-line coupling simulations have extremely low computational efficiency, while efficient frequency-domain field-to-line coupling models and algorithms are rare. A novel hybrid method integrating the finite-difference frequency-domain (FDFD) method with transmission line equations and method of moments (MoM) is developed to achieve accurate and efficient calculation of low-frequency radiation interference on MTLs in shielded enclosures. Firstly, the transmission line equations are employed to establish the low-frequency radiation coupling model of MTLs, which are then solved by the FDFD method to derive a novel FDFD-TL matrix equation. Subsequently, the accurate electric field distribution along the MTLs is calculated using the MoM in terms of avoiding directly meshing the MTLs′ fine structures, yielding the equivalent voltage source terms for the FDFD-TL matrix equation. Finally, the FDFD-TL matrix equation is rapidly solved by the complex-conjugate gradient method combined with the MPI parallelization technique to obtain the current responses along the MTLs and their terminal loads. Numerical simulations of corresponding test cases are carried out via this method and full-wave MoM, and their results are compared in terms of accuracy and computational time to validate the precision and efficiency of the proposed method.