Aedes albopictus with a worldwide distribution, has been a vector for more than 20 arboviruses such as dengue, chikugunya, Zika and West Nile, but insecticide resistance in A. albopictus has become more and more serious, as a result of improper application of pyrethroid insecticides for mosquito control. The P450 gene cluster is known to be involved in metabolic mechanisms of pyrethroid resistance in other mosquito species. However, little is known about metabolic resistance in field A. albopictus in China. In this study, we collected five different field strains and first revealed the larval and adult resistance status of A. albopictus to deltamethrin in Jiangsu province of China. A combination of comparative genomics and P450 gene cluster analysis was conducted to investigate the underlying CYP6-mediated metabolic resistance mechanisms against deltamethrin in these field mosquitoes. The significance of three CYP6 genes, AALF024122, AALF024124 and AALF018944 in deltamethrin resistance was identified in our study. Furthermore, RNA interference-mediated silencing of three genes all increased the sensitivity of mosquitoes to deltamethrin in vivo, showing that these genes may be viable biomarkers for pyre throid resistance management in field A. albopictus.