Five different weed plants viz. Convulvulus arvensis, Chenopodium murale, Tribulus terrestris, Trianthema portulacastrum, and Achyranthes aspera were investigated for their entomocidal and genotoxic effects against Culex quinquefasciatus mosquitoes. High mortality was observed at 72 hours in a dose dependent manner. Among all the tested plants, A. aspera was found highly significant which showed 100% mortality at 250 ppm after 72 hours with LC 50 of 87.46, 39.08 and 9.22 ppm at 24, 48, respectively. in combination with Bacillus thuringiensis israelensis (Bti); A. aspera also caused 100% mortality at 250 ppm concentration after 72 hours (LC 50 8.29 ppm). Phytochemical analysis of all the tested weed plants showed the presence of flavonoids, saponins, tannins, steroids, cardiac glycosides, alkaloids, anthrequinones and terpenoids. Random Amplification of Polymorphic DNA-Polymerase chain reaction (RAPD-PCR) and comet assay were performed to assess the genotoxic effect of A. aspera but no change in DNA profile was observed. Furthermore, FTIR showed the presence of phenolic compounds in A. aspera extract. It is suggested that certain phenolic compounds such as flavonoids modulate the enzymatic activity and, hence, cause the death of larvae of Cx. quinquefasciatus. Altogether, current study would serve as an initial step towards replacement of synthetic insecticides to plant-microbe based biopesticide against Culex mosquitoes in future.Mosquitoes are reported to cause nuisance to humans and transmit several viral and protozoan diseases of public health concern worldwide. These are female mosquitoes which make a bite during their search for blood meal before oviposition which thus, increases their tendency to transmit several diseases including malaria, filariasis, dengue fever, japanese encephalitis, chikungunya, zika virus and yellow fever. These diseases make life at risk of millions of people particularly in subtropical/tropical world 1,2 . Of various mosquito species, Cx. quinquefasciatus transmits various diseases i.e., West Nile virus, Japanese encephalitis, filariasis, bancroftian filariasis (Wuchereria bancrofti), St. Louis encephalitis, and avian malaria 3 . In southern United States, St. Louis virus and West Nile virus (WNV) were transmitted by Cx. quinquefasciatus 4,5 . Almost 120 million people are affected annually only by lymphatic filariasis, whereas 1.3 billion are at risk resulting in nearly $1.3 billion loss of productivity per year 6 . Similarly, three billion individuals are at risk of being infected by Japanese encephalitis with 30,000-50,000 reported cases every year in disease endemic areas 7 . Besides disease transmission in humans; Cx. quinquefasciatus is also responsible for transmitting several diseases to livestock and companion animals viz. Rift Valley fever, canine dirofilariasis (dog heartworm), avian malaria, avian pox, and West Nile encephalitis which lead to high mortalities or decreased productivity 8 . open Scientific RepoRtS | (2020) 10:6826 | https://doi.org/10.1038/s41598-020-6381...