We observe substantial amplitude anomalies of Pn waveforms that propagated through the southeastern Tarim basin and western Tien Shan along the two profiles, which are from an earthquake that occurred on the southeastern margin of Tarim basin. Although there is only a 5° difference in azimuth from the epicenter for the two profiles, the Pn amplitude differences along them are significant. The synthetic seismograms in the band of 0.5–1.5 Hz for different models along the two profiles are simulated to interpret the observed anomalies. The simulation results indicate that the Pn anomalies along the two profiles may not result from the earthquake focal mechanism or the average‐layered mantle lid structure. The Moho topography along the R–A profile may mainly account for the drastic variation of Pn amplitudes in 0.5–1.5 Hz as the epicentral distance increases from 850 to 1100 km, whereas the Moho topography and the velocity heterogeneity may together account for the observed Pn anomalies in the band of 0.5–1.5 Hz along the R–B profile.