Objective To investigate the resistance of Musca domestica to commonly used insecticides in Anshun city, Guizhou province, provide guidance in the control of M. domestica. Methods WHO recommended topical application method was used to determine the resistance levels of M. domestica to four insecticides in Xixiu district, development zone and Pingba county. The experimental data were statistically analyzed by SPSS 17.0 software. Results Musca domestica in Anshun city showed different levels of resistance to four commonly used insecticides. Statistics revealed that the resistance to propoxur could not obtain results by using topical application method, which was significantly different from the other three insecticides. The median lethal dose (LD₅₀) of the adult flies against DDVP, beta-cypemethrin, and deltamethrin were 0.526-0.739, 0.135-0.254, and 0.108-0.176 μg, and the resistance ratios were 175.33-246.33, 7.94-14.94, and 15.43-25.14, respectively; that the resistance to DDVP was the highest. Conclusion Musca domestica in Anshun city have developed resistance to the tested insecticides, especially to propoxur and DDVP. Therefore, in practice, insecticides resistance surveillance should be highlighted for wise use of insecticides.