Periodic signals replaced noise that was found in continuous seismic data, particularly in the nighttime, from the broadband seismometer at the MVP-LAI (monitoring vibrations and perturbations in the lithosphere, atmosphere and ionosphere) system before the occurrence of the Luxian earthquake on 16 September 2021. A short distance of ~150 km between the MVP-LAI system and the epicenter of the Luxian earthquake suggests the periodic singles as promising seismo-phenomena, due to that the radius of the earthquake preparation zone is ~380 km for an M6 event. Integration of geophysical parameters, including atmospheric pressure, vertical electric field, radon concentration, groundwater level and precipitation, at the MVP-LAI system provides an excellent opportunity for studying the seismo-LAI coupling associated with the Luxian earthquake. Analytical results show that ground vibrations, atmospheric pressure and total electron content varied from ~10−3 to ~10−2 Hz before the Luxian earthquake. The seismo-LAI coupling in the relatively low frequency band (~10−3 Hz) can be referred to as the acoustic-gravity waves triggered by the amplified ground vibrations. In contrast, the seismo-LAI coupling in a relatively high frequency band (~10−2 Hz) would be caused by micro-cracks and/or the high-mode natural frequency that further drives changes of TEC due to the atmospheric resonance.