Sensory appendage proteins (SAPs) serve as molecular arms of odorant-binding protein family members and mediate chemical communication from the external to the internal environment of the insect body. We recently reported that SAP members might have an important role in blood-feeding and/or insecticide resistance-associated behavioral physiologies, but the mechanism remains unclear. Here we show how SAP contributes to the host attraction during navigation for blood-feeding, and riggers an alert via integrated actions of eyes and peripheral sensory organs to circumvent the toxic effect of insecticide in the susceptible strain of An. culicifacies. Among the six identified SAP members, AcSAP1 and AcSAP2 are abundantly expressed in the olfactory and legs, and their expression is significantly modulated at night in naive adult female mosquitoes. We noticed that AcSAP1 silencing significantly impairs the host-attraction properties of the mosquitoes. Its strong binding affinity to the synthetic pyrethroid prompted us to evaluate the AcSAP1 response to insecticide exposure. Confocal microscopy and molecular profiling data reveal a heightened modulation in the expression of AcSAP1 in eyes, and other peripheral sensory organs including the olfactory, legs, and wings. These findings collectively suggest a crucial role of AcSAP1 in facilitating mosquito navigation, and/or insecticide avoidance. Unraveling the basis of SAP interactions with peripheral sensory systems could pave the way for developing novel vector control tools.