Intracontinental earthquakes usually cause severe casualties and property damage, yet their mechanism is still unclear. The TanLu Fault Zone (TLFZ) has been a typical large intracontinental strike-slip fault in eastern China since the Quaternary, which has hosted many large earthquakes (M ≥ 6). Generation of large earthquakes is generally closely related to the heterogeneities on and adjacent to the fault plane, which may result from different composition and inclusions of fluids. In this study, we use the receiver function method to obtain detailed distributions of Poisson's ratio and crustal thickness in the central-southern segment of the TLFZ, where the M 8.5 TanCheng earthquake occurred in 1668. We found that the distribution of earthquakes is strongly correlated with the crustal structures, both of which exhibit clear segmentation. The strongly damaged zone (with earthquake intensity ≥ 10) of the 1668 TanCheng earthquake and present small-to-moderate earthquakes are generally located above a segment that has shallower Moho and particularly higher Poisson's ratio. We propose that the high Poisson's ratio may be caused by intrusive mafic rocks in the ductile lower crust, which plays a role as local stress concentrators and subsequently leads to large intracontinental earthquakes.