Objective To investigate the resistance of Musca domestica to 5 commonly used insecticides in Hangzhou, and to compare the results with those of the last 20 years, providing scientific basis for prevention and control. Methods Musca domestica were collected from Jiande city, Jianggan district and Xiacheng district of Hangzhou city from June to July, 2014. Topical application was used to determine the resistance of M. domestica to 5 commonly used insecticides. Results The resistance to propoxur was the highest, the resistances ratios (R/R)>1 345. The resistances ratios to deltamethrin, beta-cypermethrin, dichlorvos, and three chlorine insecticidal ester was 77.33(LD₅₀=0.069 6 μg/♀), 55.58 (LD₅₀=0.200 1 μg/♀), 7.26(LD₅₀=0.329 0 μg/♀), and 6.79(LD₅₀=1.460 8 μg/♀), respectively. The monitoring data showed that the resistance to deltamethrin and beta-cypermethrin were at a high level; the resistance to dichlorvos showed an increasing trend year by year, the highest in 2008, and then declined; the resistance to propoxur increased sharply, the resistance to three chlorine insecticidal ester showed a rising trend. Conclusion The M. domestica strains of Hangzhou have been resistant to many kinds of insecticides. Some insecticides, such as propoxur, have been ineffective. Sustainable integrated response strategies should be established in M. domestica control in Hangzhou. In order to slow down or prevent resistance, environmental control and physical control should be considered as the main control means; if necessary, chemical insecticides with low resistance can be selected based on the resistance monitoring data.