Southwest Yunnan, located in the southern segment of the north-south seismic belt, is one of the regions with strong tectonic movement and seismic activity in China. Study on the characteristics of tectonic setting and deep geophysical field in the region is an important issue in basic science. In 2013, we conducted a 600-km-long Menghai-Gengma-Lushui profile of deep seismic wide-angle reflection/refraction and high-resolution seismic refraction in Southwest Yunnan. In this paper, we use 6 groups of clear intracrustal P-wave phases picked from the seismic record sections of 11 shots to build a velocity structure model of basement and 2D crustal P-wave of the region by using finite difference inversion and ray travel time forward fitting technology. The results show that, from south to north, the crust gradually thickens along the profile and its basement shows a significant lateral heterogeneity. In the vicinity of the Nanting River fault, the basement structure shows the character of alternate depressions and uplifts, and the shallowest basement is about 1.0 km. In the vicinity of Tengchong and Lancang, the basement is about 5.0 km deep. The velocity of the middle and lower crust in the region generally increases with the increasing of depth. At the block boundary and beneath the fault tectonic belt, the velocity contours show apparent irregularity and the P-wave velocity changes sharply. In this region, the Moho gradually deepens from south to north with relatively large lateral undulations. The shallowest point of the Moho is located near Menghai at a depth of about 32.0 km. The deepest point of the Moho is located near Tengchong at a depth of about 40.5 km. Between Gengma and Yongde, the Moho shows significantly fast uplifting and depressing with an amplitude of about 4.0 km. Beneath the Nanting River fault, Longling-Ruili fault, Dayingjiang fault and Tengchong volcano, the basement velocity structure, 2D crustal P-wave velocity structure, distribution of average profile velocity and intracrustal interface spreading also show significant changes from the basement to the top of the Moho, indicating that the crustal velocity and medium physical properties beneath the fault tectonic belt are apparently different from the crustal materials on its both sides, which suggests that these faults should be in a certain scale and may extend to the lower crust or the top of the upper mantle. The earthquakes in the region mainly occurred at a depth of 10–20 km, and the seismic activity is related to the intracrustal medium velocity difference and fault belt distribution. The results can serve as the important data of the crust-mantle structure for the analysis of the deep tectonic setting, earthquake precise positioning, seismogenic structure modeling of the seismic activities in Southwest Yunnan, as well as the important reference for the evaluation of seismic hazard and the planning of earthquake disaster mitigation of this region. Southwest Yunnan, located in the southern segment of the north-south seismic belt, is one of the regions with strong tectonic movement and seismic activity in China. Study on the characteristics of tectonic setting and deep geophysical field in the region is an important issue in basic science. In 2013, we conducted a 600-km-long Menghai-Gengma-Lushui profile of deep seismic wide-angle reflection / refraction and high-resolution seismic refraction in Southwest Yunnan. In this paper, we use 6 groups of clear intracrustal P-wave phases picked from the seismic record sections of 11 shots to build a velocity structure model of basement and 2D crustal P-wave of the region by using finite difference inversion and ray travel time forward fitting technology. The results show that, from south to north, the crust gradually thickens along the profile and its basement shows a significant lateral heterogeneity. In the vicinity of the Nanting River fault, the basement structure shows the character of alternate depressions and uplifts, and the shallowest basement is about 1.0 km. In the vicinity of Tengchong and Lancang, the basement is about 5.0 km deep. The velocity of the middle and lower crust in the region generally increases with the increasing of depth. At the block boundary and beneath the fault tectonic belt, the velocity contours show apparent irregularity and the P-wave velocity changes sharply. In this region, the Moho gradually deepens from south to north with relatively large lateral undulations. The shallowest point of the Moho is The deepest point of the Moho is located near Tengchong at a depth of about 40.5 km. Between Gengma and Yongde, the Moho shows significantly fast uplifting and depressing with amplitude of about 4.0 km. Beneath the Nanting River fault, Longling-Ruili fault, Dayingjiang fault and Tengchong volcano, the basement velocity structure, 2D crustal P-wave velocity structure, distribution of average profile velocity and intracrustal interface spreading also show significant changes from the basement to the top of the Moho, indicating that the crustal velocity and medium physical properties beneath the fault tectonic belt are apparently different from the crustal materials on its both sides, which suggests that these faults should be in a certain scale and may extend to the lower crust or the top of the upper mantle. The earthquakes in the region due to a depth of 10-20 km, and the seismic activity is related to the intracrustal medium velocity difference and fault belt distribution. The results can serve as the important data of the crust-mantle structure for the analysis of the deep tectonic setting, earthquake precise positioning, seismogenic structure modeling of the seismic activities in Southwest Yunnan, as well as the important reference for the evaluation of seismic hazard and the planning of earthquake disaster mitigation of this region.