Abstract: This paper collected the seismic travel-time data both from temporary stations employed after Yangbi M6.4 earthquake and the seismic networks in Yangbi region and its vicinity from January of 2015 to 28 May, 2021 and performed the high-resolution inversion for three-dimensional velocity structure and accurate hypocentral locations by using double-difference seismic tomography method. The relocation results show that the sequence spread in the NW−SE direction along the Weixi-Qiaohou-Weishan fault. The focal depth in the area is generally in the range of 2−5 km with high dip angle of 80°. The three-dimensional velocity structure shows that the spatial distribution characteristics of the Yangbi M6.4 earthquake sequence are closely related to the velocity structure. The epicenter of the Yangbi M6.4 main shock was located near the P- and S-wave high-to-low-velocity anomaly transitional zones, which are favorable for occurrence of moderate-strong earthquakes, and the aftershocks are mainly distributed in the brittle region with low v_P, high v_S and low v_P/v_S. In addition, along the strike of Yangbi earthquake sequence, there are totally different velocity structures on both sides of main earthquake, and significant higher v_P and lower v_S anomalies are observed in the northwest of the Yangbi M6.4 main shock compared with the southeast part, which may obstruct the northwestward slipping of the seismogenic fault of Yangbi M6.4 earthquake, leading to the striking unilateral source rupture.