The 1654 Lixian M8 earthquake occurred in the northeastern margin of the Qinghai-Tibet Plateau with strong Neotectonic activity. The earthquake stricken area is located in the mid-north segment of the South-North seismic belt, where many active faults are developed. The M8 earthquake occurred in the loess area about 370 years ago. Affected by natural erosion and human activities, its surface rupture zone and secondary disasters are now difficult to distinguish. Many seismologists have done a lot of research work on the earthquake, and there are different understandings and opinions on its seismogenic fault. Therefore, based on the observation data of seismic network and mobile network since 1970, this paper studied the seismogenic structure of the Lixian M8 earthquake in 1654 by using the seismic tomography method and joint inversion calculation. According to the distribution of small earthquake activities along the Minxian-Lixian-Liangdang line, it was speculated that the "Minxian-Lixian-Liangdang fault" may be the seismogenic fault of the Lixian M8 earthquake in 1654, but further study of field geological work is still needed.